{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:02:18Z","timestamp":1779786138680,"version":"3.53.1"},"reference-count":198,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Pharmacol Sin"],"DOI":"10.1038\/s41401-026-01814-9","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:48:34Z","timestamp":1779778114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["T cell-targeted immunotherapies for multiple sclerosis: molecular mechanisms to therapeutic perspectives from Traditional Chinese medicine"],"prefix":"10.1038","author":[{"given":"Meiling","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenyu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaohui","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"1814_CR1","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/S0140-6736(02)08220-X","volume":"359","author":"A Compston","year":"2002","unstructured":"Compston A, Coles A. Multiple sclerosis. Lancet. 2002;359:1221\u201331.","journal-title":"Lancet"},{"key":"1814_CR2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature04753","volume":"441","author":"E Bettelli","year":"2006","unstructured":"Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441:235\u20138.","journal-title":"Nature"},{"key":"1814_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103312","volume":"22","author":"FF Konen","year":"2023","unstructured":"Konen FF, Mohn N, Witte T, Schefzyk M, Wiestler M, Lovric S, et al. Treatment of autoimmunity: the impact of disease-modifying therapies in multiple sclerosis and comorbid autoimmune disorders. Autoimmun Rev. 2023;22:103312.","journal-title":"Autoimmun Rev"},{"key":"1814_CR4","doi-asserted-by":"publisher","first-page":"259","DOI":"10.2147\/nedt.2007.3.2.259","volume":"3","author":"A Tselis","year":"2007","unstructured":"Tselis A, Khan O, Lisak RP. Glatiramer acetate in the treatment of multiple sclerosis. Neuropsychiatr Dis Treat. 2007;3:259\u201367.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"1814_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s40893-017-0024-4","volume":"2","author":"P Gallo","year":"2017","unstructured":"Gallo P, Centonze D, Marrosu MG. Alemtuzumab for multiple sclerosis: the new concept of immunomodulation. Mult Scler Demyelinating Disord. 2017;2:7.","journal-title":"Mult Scler Demyelinating Disord"},{"key":"1814_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1509956","volume":"15","author":"Y Bulliard","year":"2024","unstructured":"Bulliard Y, Freeborn R, Uyeda MJ, Humes D, Bjordahl R, de Vries D, et al. From promise to practice: CAR T and Treg cell therapies in autoimmunity and other immune-mediated diseases. Front Immunol. 2024;15:1509956.","journal-title":"Front Immunol"},{"key":"1814_CR7","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.expneurol.2015.11.010","volume":"277","author":"K Ohl","year":"2016","unstructured":"Ohl K, Tenbrock K, Kipp M. Oxidative stress in multiple sclerosis: central and peripheral mode of action. Exp Neurol. 2016;277:58\u201367.","journal-title":"Exp Neurol"},{"key":"1814_CR8","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.cmet.2020.07.001","volume":"32","author":"T Alissafi","year":"2020","unstructured":"Alissafi T, Kalafati L, Lazari M, Filia A, Kloukina I, Manifava M, et al. Mitochondrial oxidative damage underlies regulatory T cell defects in autoimmunity. Cell Metab. 2020;32:591\u2013604.e7.","journal-title":"Cell Metab"},{"key":"1814_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103240","volume":"75","author":"M Wu","year":"2024","unstructured":"Wu M, Yu S, Yan S, Wu M, Zhang L, Chen S, et al. Peroxynitrite reduces Treg cell expansion and function by mediating IL-2R nitration and aggravates multiple sclerosis pathogenesis. Redox Biol. 2024;75:103240.","journal-title":"Redox Biol"},{"key":"1814_CR10","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2767208","volume":"2018","author":"XC Peng","year":"2018","unstructured":"Peng XC, Huang JR, Wang SW, Liu L, Liu ZZ, Sethi G, et al. Traditional Chinese medicine in neuroprotection after brain insults with special reference to radioprotection. Evid Based Complement Altern Med. 2018;2018:2767208.","journal-title":"Evid Based Complement Altern Med"},{"key":"1814_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1629288","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang Y, Bu P, Deng Y, Zhao W, Pan G. Research progress on traditional Chinese medicine compounds in autoimmune-related skin diseases. Front Immunol. 2025;16:1629288.","journal-title":"Front Immunol"},{"key":"1814_CR12","first-page":"4163","volume":"17","author":"Q Li","year":"2018","unstructured":"Li Q, Yang T, Guo AC, Fan YP. Role of catalpol in ameliorating the pathogenesis of experimental autoimmune encephalomyelitis by increasing the level of noradrenaline in the locus coeruleus. Mol Med Rep. 2018;17:4163\u201372.","journal-title":"Mol Med Rep"},{"key":"1814_CR13","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7074157","volume":"2022","author":"M Wu","year":"2022","unstructured":"Wu M, Kang Q, Kang Y, Tong Y, Yang T, Fan Y. Catalpol Regulates oligodendrocyte regeneration and remyelination by activating the GEF-Cdc42\/Rac1 signaling pathway in EAE mice. Evid Based Complement Altern Med. 2022;2022:7074157.","journal-title":"Evid Based Complement Altern Med"},{"key":"1814_CR14","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.freeradbiomed.2019.10.408","volume":"146","author":"W Li","year":"2020","unstructured":"Li W, Deng R, Jing X, Chen J, Yang D, Shen J. Acteoside ameliorates experimental autoimmune encephalomyelitis through inhibiting peroxynitrite-mediated mitophagy activation. Free Radic Biol Med. 2020;146:79\u201391.","journal-title":"Free Radic Biol Med"},{"key":"1814_CR15","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.taap.2018.10.024","volume":"362","author":"L Yang","year":"2019","unstructured":"Yang L, Xing F, Han X, Li Q, Wu H, Shi H, et al. Astragaloside IV regulates differentiation and induces apoptosis of activated CD4+ T cells in the pathogenesis of experimental autoimmune encephalomyelitis. Toxicol Appl Pharmacol. 2019;362:105\u201315.","journal-title":"Toxicol Appl Pharmacol"},{"key":"1814_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1619581","volume":"16","author":"J Zhao","year":"2025","unstructured":"Zhao J, Zhang W. Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism. Front Pharmacol. 2025;16:1619581.","journal-title":"Front Pharmacol"},{"key":"1814_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113180","volume":"151","author":"Z Bi","year":"2022","unstructured":"Bi Z, Zhang W, Yan X. Anti-inflammatory and immunoregulatory effects of icariin and icaritin. Biomed Pharmacother. 2022;151:113180.","journal-title":"Biomed Pharmacother"},{"key":"1814_CR18","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.neulet.2016.01.008","volume":"619","author":"Z Dong","year":"2016","unstructured":"Dong Z, Ma D, Gong Y, Yu T, Yao G. Salvianolic acid B ameliorates CNS autoimmunity by suppressing Th1 responses. Neurosci Lett. 2016;619:92\u20139.","journal-title":"Neurosci Lett"},{"key":"1814_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107452","volume":"207","author":"L Zhang","year":"2020","unstructured":"Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther. 2020;207:107452.","journal-title":"Pharmacol Ther"},{"key":"1814_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/srep41887","volume":"7","author":"H Zhang","year":"2017","unstructured":"Zhang H, Qi Y, Yuan Y, Cai L, Xu H, Zhang L, et al. Paeoniflorin ameliorates experimental autoimmune encephalomyelitis via inhibition of dendritic cell function and Th17 cell differentiation. Sci Rep. 2017;7:41887.","journal-title":"Sci Rep"},{"key":"1814_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1425731","volume":"15","author":"R Yang","year":"2024","unstructured":"Yang R, Wang R, Xu A, Zhang J, Ma J. Mitigating neurodegenerative diseases: the protective influence of baicalin and baicalein through neuroinflammation regulation. Front Pharmacol. 2024;15:1425731.","journal-title":"Front Pharmacol"},{"key":"1814_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/srep17407","volume":"5","author":"Y Zhang","year":"2015","unstructured":"Zhang Y, Li X, Ciric B, Ma CG, Gran B, Rostami A, et al. Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway. Sci Rep. 2015;5:17407.","journal-title":"Sci Rep"},{"key":"1814_CR23","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/1472-6882-12-64","volume":"12","author":"J Yang","year":"2012","unstructured":"Yang J, Yang X, Li M. Baicalin, a natural compound, promotes regulatory T cell differentiation. BMC Complement Altern Med. 2012;12:64.","journal-title":"BMC Complement Altern Med"},{"key":"1814_CR24","doi-asserted-by":"publisher","first-page":"e17164","DOI":"10.1371\/journal.pone.0017164","volume":"6","author":"J Yang","year":"2011","unstructured":"Yang J, Yang X, Chu Y, Li M. Identification of baicalin as an immunoregulatory compound by controlling Th17 cell differentiation. PLoS ONE. 2011;6:e17164.","journal-title":"PLoS ONE"},{"key":"1814_CR25","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/s41423-019-0221-5","volume":"16","author":"L Van Kaer","year":"2019","unstructured":"Van Kaer L, Postoak JL, Wang C, Yang G, Wu L. Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE. Cell Mol Immunol. 2019;16:531\u20139.","journal-title":"Cell Mol Immunol"},{"key":"1814_CR26","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1177\/1352458514521312","volume":"20","author":"T Owens","year":"2014","unstructured":"Owens T. The complex immunology of multiple sclerosis. Mult Scler. 2014;20:1023\u20134.","journal-title":"Mult Scler"},{"key":"1814_CR27","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/s41577-022-00718-z","volume":"22","author":"KE Attfield","year":"2022","unstructured":"Attfield KE, Jensen LT, Kaufmann M, Friese MA, Fugger L. The immunology of multiple sclerosis. Nat Rev Immunol. 2022;22:734\u201350.","journal-title":"Nat Rev Immunol"},{"key":"1814_CR28","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/j.1600-065X.2011.01016.x","volume":"241","author":"JM Goverman","year":"2011","unstructured":"Goverman JM. Immune tolerance in multiple sclerosis. Immunol Rev. 2011;241:228\u201340.","journal-title":"Immunol Rev"},{"key":"1814_CR29","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1093\/brain\/awp289","volume":"132","author":"V Brucklacher-Waldert","year":"2009","unstructured":"Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E. Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain. 2009;132:3329\u201341.","journal-title":"Brain"},{"key":"1814_CR30","doi-asserted-by":"crossref","unstructured":"Segal BM. The diversity of encephalitogenic CD4+ T cells in multiple sclerosis and its animal models. J Clin Med. 2019;8:120.","DOI":"10.3390\/jcm8010120"},{"key":"1814_CR31","doi-asserted-by":"crossref","unstructured":"Danikowski KM, Jayaraman S, Prabhakar BS. Regulatory T cells in multiple sclerosis and myasthenia gravis. J Neuroinflammation 2017;14:117.","DOI":"10.1186\/s12974-017-0892-8"},{"key":"1814_CR32","doi-asserted-by":"crossref","unstructured":"Kaskow BJ, Baecher-Allan C. Effector T cells in multiple sclerosis. Cold Spring Harb Perspect Med. 2018;8:a029025.","DOI":"10.1101\/cshperspect.a029025"},{"key":"1814_CR33","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1080\/08923973.2024.2330642","volume":"46","author":"M Aliyu","year":"2024","unstructured":"Aliyu M, Zohora FT, Ceylan A, Hossain F, Yazdani R, Azizi G. Immunopathogenesis of multiple sclerosis: molecular and cellular mechanisms and new immunotherapeutic approaches. Immunopharmacol Immunotoxicol. 2024;46:355\u201377.","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"1814_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102027","volume":"6","author":"I Jelcic","year":"2025","unstructured":"Jelcic I, Naghavian R, Fanaswala I, Macnair W, Esposito C, Calini D, et al. T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis. Cell Rep Med. 2025;6:102027.","journal-title":"Cell Rep Med"},{"key":"1814_CR35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.665718","volume":"12","author":"C Veroni","year":"2021","unstructured":"Veroni C, Aloisi F. The CD8 T cell-epstein-Barr virus-B cell trialogue: a central issue in multiple sclerosis pathogenesis. Front Immunol. 2021;12:665718.","journal-title":"Front Immunol"},{"key":"1814_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102647","volume":"19","author":"T Moser","year":"2020","unstructured":"Moser T, Akgun K, Proschmann U, Sellner J, Ziemssen T. The role of TH17 cells in multiple sclerosis: therapeutic implications. Autoimmun Rev. 2020;19:102647.","journal-title":"Autoimmun Rev"},{"key":"1814_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-3083.2011.02536.x","volume":"74","author":"F Jadidi-Niaragh","year":"2011","unstructured":"Jadidi-Niaragh F, Mirshafiey A. Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol. 2011;74:1\u201313.","journal-title":"Scand J Immunol"},{"key":"1814_CR38","doi-asserted-by":"publisher","first-page":"7768","DOI":"10.4049\/jimmunol.176.12.7768","volume":"176","author":"A Vaknin-Dembinsky","year":"2006","unstructured":"Vaknin-Dembinsky A, Balashov K, Weiner HL. IL-23 is increased in dendritic cells in multiple sclerosis and the downregulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J Immunol. 2006;176:7768\u201374.","journal-title":"J Immunol"},{"key":"1814_CR39","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s11481-009-9188-9","volume":"5","author":"M El-behi","year":"2010","unstructured":"El-behi M, Rostami A, Ciric B. Current views on the roles of Th1 and Th17 cells in experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol. 2010;5:189\u201397.","journal-title":"J Neuroimmune Pharmacol"},{"key":"1814_CR40","doi-asserted-by":"crossref","unstructured":"Kunkl M, Frascolla S, Amormino C, Volpe E, Tuosto L. T helper cells: the modulators of inflammation in multiple sclerosis. Cells. 2020;9:482.","DOI":"10.3390\/cells9020482"},{"key":"1814_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-63877-0","volume":"14","author":"SM Milne","year":"2024","unstructured":"Milne SM, Lahiri A, Sanchez CL, Marshall MJ, Jahan I, Meares GP. Myelin oligodendrocyte glycoprotein reactive Th17 cells drive Janus Kinase 1 dependent transcriptional reprogramming in astrocytes and alter cell surface cytokine receptor profiles during experimental autoimmune encephalomyelitis. Sci Rep. 2024;14:13146.","journal-title":"Sci Rep"},{"key":"1814_CR42","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.humimm.2020.02.009","volume":"81","author":"R Balasa","year":"2020","unstructured":"Balasa R, Barcutean L, Balasa A, Motataianu A, Roman-Filip C, Manu D. The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum Immunol. 2020;81:237\u201343.","journal-title":"Hum Immunol"},{"key":"1814_CR43","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s40120-018-0120-1","volume":"8","author":"J Aram","year":"2019","unstructured":"Aram J, Francis A, Tanasescu R, Constantinescu CS. Granulocyte-macrophage colony-stimulating factor as a therapeutic target in multiple sclerosis. Neurol Ther. 2019;8:45\u201357.","journal-title":"Neurol Ther"},{"key":"1814_CR44","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/nm1651","volume":"13","author":"H Kebir","year":"2007","unstructured":"Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 2007;13:1173\u20135.","journal-title":"Nat Med"},{"key":"1814_CR45","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/nature05505","volume":"445","author":"Y Zheng","year":"2007","unstructured":"Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a Th17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445:648\u201351.","journal-title":"Nature"},{"key":"1814_CR46","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1038\/sj.cr.7310106","volume":"16","author":"Y Chung","year":"2006","unstructured":"Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C. Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res. 2006;16:902\u20137.","journal-title":"Cell Res"},{"key":"1814_CR47","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1084\/jem.20061308","volume":"203","author":"SC Liang","year":"2006","unstructured":"Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance the expression of antimicrobial peptides. J Exp Med. 2006;203:2271\u20139.","journal-title":"J Exp Med"},{"key":"1814_CR48","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nri2343","volume":"8","author":"DA Vignali","year":"2008","unstructured":"Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8:523\u201332.","journal-title":"Nat Rev Immunol"},{"key":"1814_CR49","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","volume":"133","author":"S Sakaguchi","year":"2008","unstructured":"Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775\u201387.","journal-title":"Cell"},{"key":"1814_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21861-5","volume":"8","author":"M Sambucci","year":"2018","unstructured":"Sambucci M, Gargano F, De Rosa V, De Bardi M, Picozza M, Placido R, et al. FoxP3 isoforms and PD-1 expression by T regulatory cells in multiple sclerosis. Sci Rep. 2018;8:3674.","journal-title":"Sci Rep"},{"key":"1814_CR51","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41577-024-00994-x","volume":"24","author":"TS Sumida","year":"2024","unstructured":"Sumida TS, Cheru NT, Hafler DA. The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nat Rev Immunol. 2024;24:503\u201317.","journal-title":"Nat Rev Immunol"},{"key":"1814_CR52","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/j.1365-2567.2007.02690.x","volume":"123","author":"K Venken","year":"2008","unstructured":"Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens JL, et al. Compromised CD4+ CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology. 2008;123:79\u201389.","journal-title":"Immunology"},{"key":"1814_CR53","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.molmed.2009.12.003","volume":"16","author":"K Venken","year":"2010","unstructured":"Venken K, Hellings N, Liblau R, Stinissen P. Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol Med. 2010;16:58\u201368.","journal-title":"Trends Mol Med"},{"key":"1814_CR54","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200251","volume":"11","author":"T Lorenzini","year":"2024","unstructured":"Lorenzini T, Faigle W, Ruder J, Docampo MJ, Opitz L, Martin R. Alterations of thymus-derived Tregs in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11:e200251.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"1814_CR55","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1007\/s12031-016-0789-5","volume":"60","author":"Z Etesam","year":"2016","unstructured":"Etesam Z, Nemati M, Ebrahimizadeh MA, Ebrahimi HA, Hajghani H, Khalili T, et al. Altered expression of specific transcription factors of Th17 (RORgammat, RORalpha) and Treg Lymphocytes (FOXP3) by peripheral blood mononuclear cells from patients with multiple sclerosis. J Mol Neurosci. 2016;60:94\u2013101.","journal-title":"J Mol Neurosci"},{"key":"1814_CR56","doi-asserted-by":"publisher","first-page":"711","DOI":"10.3389\/fimmu.2019.00711","volume":"10","author":"I Wimmer","year":"2019","unstructured":"Wimmer I, Tietz S, Nishihara H, Deutsch U, Sallusto F, Gosselet F, et al. PECAM-1 stabilizes blood-brain barrier integrity and favors paracellular T-cell diapedesis across the blood-brain barrier during neuroinflammation. Front Immunol. 2019;10:711.","journal-title":"Front Immunol"},{"key":"1814_CR57","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s00702-005-0409-y","volume":"113","author":"B Engelhardt","year":"2006","unstructured":"Engelhardt B. Molecular mechanisms involved in T cell migration across the blood-brain barrier. J Neural Transm. 2006;113:477\u201385.","journal-title":"J Neural Transm"},{"key":"1814_CR58","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1101379","volume":"17","author":"G Angelini","year":"2023","unstructured":"Angelini G, Bani A, Constantin G, Rossi B. The interplay between T helper cells and brain barriers in the pathogenesis of multiple sclerosis. Front Cell Neurosci. 2023;17:1101379.","journal-title":"Front Cell Neurosci"},{"key":"1814_CR59","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/eji.202149238","volume":"52","author":"L Marchetti","year":"2022","unstructured":"Marchetti L, Francisco D, Soldati S, Haghayegh Jahromi N, Barcos S, Gruber I, et al. ACKR1 favors transcellular over paracellular T-cell diapedesis across the blood-brain barrier in neuroinflammation in vitro. Eur J Immunol. 2022;52:161\u201377.","journal-title":"Eur J Immunol"},{"key":"1814_CR60","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.3389\/fimmu.2019.03056","volume":"10","author":"N Haghayegh Jahromi","year":"2019","unstructured":"Haghayegh Jahromi N, Marchetti L, Moalli F, Duc D, Basso C, Tardent H, et al. Intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 differentially contribute to peripheral activation and CNS entry of autoaggressive Th1 and Th17 cells in experimental autoimmune encephalomyelitis. Front Immunol. 2019;10:3056.","journal-title":"Front Immunol"},{"key":"1814_CR61","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2153534","volume":"18","author":"J Verreycken","year":"2022","unstructured":"Verreycken J, Baeten P, Broux B. Regulatory T cell therapy for multiple sclerosis: breaching (blood-brain) barriers. Hum Vaccin Immunother. 2022;18:2153534.","journal-title":"Hum Vaccin Immunother"},{"key":"1814_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03069-9","volume":"21","author":"CE Hansen","year":"2024","unstructured":"Hansen CE, Kamermans A, Mol K, Berve K, Rodriguez-Mogeda C, Fung WK, et al. Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis. J Neuroinflammation. 2024;21:72.","journal-title":"J Neuroinflammation"},{"key":"1814_CR63","doi-asserted-by":"crossref","unstructured":"Prapas P, Anagnostouli M. Macrophages and HLA-class II alleles in multiple sclerosis: insights in therapeutic dynamics. Int J Mol Sci. 2024;25:7354.","DOI":"10.3390\/ijms25137354"},{"key":"1814_CR64","doi-asserted-by":"crossref","unstructured":"Yamasaki R. Microglia\/Macrophages in autoimmune demyelinating encephalomyelitis (multiple sclerosis\/neuromyelitis optica. Int J Mol Sci. 2025;26:3585.","DOI":"10.3390\/ijms26083585"},{"key":"1814_CR65","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/s41582-019-0253-6","volume":"15","author":"Y Dong","year":"2019","unstructured":"Dong Y, Yong VW. When encephalitogenic T cells collaborate with microglia in multiple sclerosis.\u00a0Nat Rev Neurol. 2019;15:704-17.","journal-title":"Nat Rev Neurol"},{"key":"1814_CR66","doi-asserted-by":"crossref","unstructured":"Santacreu-Vilaseca M, Moreno-Magallon J, Juanes-Casado A, Gil-S\u00e1nchez A, Gonz\u00e1lez-Mingot C, Torres P et al. Novel cell models to study myelin and microglia interactions. Int J Mol Sci. 2025;26:2179.","DOI":"10.3390\/ijms26052179"},{"key":"1814_CR67","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/708659","volume":"2013","author":"GG Ortiz","year":"2013","unstructured":"Ortiz GG, Pacheco-Moises FP, Bitzer-Quintero OK, Ramirez-Anguiano AC, Flores-Alvarado LJ, Ramirez-Ramirez V, et al. Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin Dev Immunol. 2013;2013:708659.","journal-title":"Clin Dev Immunol"},{"key":"1814_CR68","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1002\/glia.24148","volume":"70","author":"MK Sen","year":"2022","unstructured":"Sen MK, Mahns DA, Coorssen JR, Shortland PJ. The roles of microglia and astrocytes in phagocytosis and myelination: insights from the cuprizone model of multiple sclerosis. Glia. 2022;70:1215\u201350.","journal-title":"Glia"},{"key":"1814_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102439","volume":"45","author":"JR Ciotti","year":"2020","unstructured":"Ciotti JR, Valtcheva MV, Cross AH. Effects of MS disease-modifying therapies on responses to vaccinations: a review. Mult Scler Relat Disord. 2020;45:102439.","journal-title":"Mult Scler Relat Disord"},{"key":"1814_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111826","volume":"131","author":"J Canto-Gomes","year":"2024","unstructured":"Canto-Gomes J, Boleixa D, Teixeira C, Martins da Silva A, Gonzalez-Suarez I, Cerqueira J, et al. Distinct disease-modifying therapies are associated with different blood immune cell profiles in people with relapsing-remitting multiple sclerosis. Int Immunopharmacol. 2024;131:111826.","journal-title":"Int Immunopharmacol"},{"key":"1814_CR71","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.amjmed.2020.05.049","volume":"133","author":"SL Hauser","year":"2020","unstructured":"Hauser SL, Cree BAC. Treatment of multiple sclerosis: a review. Am J Med. 2020;133:1380\u201390.e2.","journal-title":"Am J Med"},{"key":"1814_CR72","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1002\/ana.410400606","volume":"40","author":"D Leppert","year":"1996","unstructured":"Leppert D, Waubant E, Burk MR, Oksenberg JR, Hauser SL. Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol. 1996;40:846\u201352.","journal-title":"Ann Neurol"},{"key":"1814_CR73","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1212\/WNL.0b013e3181c97d99","volume":"74","author":"S Dhib-Jalbut","year":"2010","unstructured":"Dhib-Jalbut S, Marks S. Interferon-beta mechanisms of action in multiple sclerosis. Neurology. 2010;74:S17\u201324.","journal-title":"Neurology"},{"key":"1814_CR74","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1177\/135245859700300609","volume":"3","author":"S Dhib-Jalbut","year":"1997","unstructured":"Dhib-Jalbut S. Mechanisms of interferon beta action in multiple sclerosis. Mult Scler. 1997;3:397\u2013401.","journal-title":"Mult Scler"},{"key":"1814_CR75","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1212\/WNL.50.5.1294","volume":"50","author":"RA Rudick","year":"1998","unstructured":"Rudick RA, Ransohoff RM, Lee JC, Peppler R, Yu M, Mathisen PM, et al. In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis. Neurology. 1998;50:1294\u2013300.","journal-title":"Neurology"},{"key":"1814_CR76","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0165-5728(00)00403-3","volume":"112","author":"Z Liu","year":"2001","unstructured":"Liu Z, Pelfrey CM, Cotleur A, Lee JC, Rudick RA. Immunomodulatory effects of interferon beta-1a in multiple sclerosis. J Neuroimmunol. 2001;112:153\u201362.","journal-title":"J Neuroimmunol"},{"key":"1814_CR77","doi-asserted-by":"publisher","first-page":"5391","DOI":"10.1007\/s10072-025-08377-3","volume":"46","author":"M Simone","year":"2025","unstructured":"Simone M, Palumbi R, Achille M, Micella S, Pascali M, Peschechera A, et al. A multicentre, prospective, randomized, open-label pragmatic trial to compare the effectiveness and safety of interferon beta-1a and glatiramer-acetate in pediatric patients affected by multiple sclerosis. Neurol Sci. 2025;46:5391\u2013400.","journal-title":"Neurol Sci"},{"key":"1814_CR78","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1606146","volume":"16","author":"S Bi","year":"2025","unstructured":"Bi S, Liu S, Zhu K, Gao D, Chen L, Yu C, et al. Preclinical and experimental evidence of salvianolic acid B in the treatment of neurological diseases. Front Pharmacol. 2025;16:1606146.","journal-title":"Front Pharmacol"},{"key":"1814_CR79","doi-asserted-by":"crossref","unstructured":"Prod'homme T, Zamvil SS. The evolving mechanisms of action of glatiramer acetate. Cold Spring Harb Perspect Med. 2019;9:a029249.","DOI":"10.1101\/cshperspect.a029249"},{"key":"1814_CR80","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1124\/pharmrev.124.000927","volume":"76","author":"R Aharoni","year":"2024","unstructured":"Aharoni R, Milo R, Arnon R. Glatiramer acetate for the treatment of multiple sclerosis: from first-generation therapy to elucidation of immunomodulation and repair. Pharmacol Rev. 2024;76:1133\u201358.","journal-title":"Pharmacol Rev"},{"key":"1814_CR81","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s40263-013-0117-3","volume":"27","author":"LJ Scott","year":"2013","unstructured":"Scott LJ. Glatiramer acetate: a review of its use in patients with relapsing-remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis. CNS Drugs. 2013;27:971\u201388.","journal-title":"CNS Drugs"},{"key":"1814_CR82","doi-asserted-by":"crossref","unstructured":"Yamout B, Alroughani R, Mohamed SFA, Al-Mahdawi AM, Khoury SJ, El Ayoubi N, et al. Comparative effectiveness of natalizumab and anti-CD20 monoclonal antibodies in relapsing-remitting multiple sclerosis: a real-world propensity-score matched study. J Neurol Neurosurg Psychiatry 2025;0:1\u20137","DOI":"10.1136\/jnnp-2024-335704"},{"key":"1814_CR83","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1002\/acn3.70122","volume":"12","author":"F Shahzad","year":"2025","unstructured":"Shahzad F, Rasheed T, Siddiqui MR, Hamid H, Khalid MB, Shabbir H, et al. The comparative effectiveness and tolerability of sphingosine-1-phosphate receptor modulators in patients with multiple sclerosis: a network meta-analysis of randomized controlled trials. Ann Clin Transl Neurol. 2025;12:2002\u201311.","journal-title":"Ann Clin Transl Neurol"},{"key":"1814_CR84","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/S0140-6736(21)00244-0","volume":"398","author":"MP McGinley","year":"2021","unstructured":"McGinley MP, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet. 2021;398:1184\u201394.","journal-title":"Lancet"},{"key":"1814_CR85","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1002\/acn3.52017","volume":"11","author":"PK Coyle","year":"2024","unstructured":"Coyle PK, Freedman MS, Cohen BA, Cree BAC, Markowitz CE. Sphingosine 1-phosphate receptor modulators in multiple sclerosis treatment: a practical review. Ann Clin Transl Neurol. 2024;11:842\u201355.","journal-title":"Ann Clin Transl Neurol"},{"key":"1814_CR86","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s40263-013-0118-2","volume":"27","author":"KP Garnock-Jones","year":"2013","unstructured":"Garnock-Jones KP. Teriflunomide: a review of its use in relapsing multiple sclerosis. CNS Drugs. 2013;27:1103\u201323.","journal-title":"CNS Drugs"},{"key":"1814_CR87","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1056\/NEJMoa1014656","volume":"365","author":"P O\u2019Connor","year":"2011","unstructured":"O\u2019Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293\u2013303.","journal-title":"N Engl J Med"},{"key":"1814_CR88","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.1093\/hmg\/ddx167","volume":"26","author":"G Hayashi","year":"2017","unstructured":"Hayashi G, Jasoliya M, Sahdeo S, Sacca F, Pane C, Filla A, et al. Dimethyl fumarate mediates Nrf2-dependent mitochondrial biogenesis in mice and humans. Hum Mol Genet. 2017;26:2864\u201373.","journal-title":"Hum Mol Genet"},{"key":"1814_CR89","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1391949","volume":"15","author":"ADR Lima","year":"2024","unstructured":"Lima ADR, Ferrari BB, Pradella F, Carvalho RM, Rivero SLS, Quintiliano RPS, et al. Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis. Front Immunol. 2024;15:1391949.","journal-title":"Front Immunol"},{"key":"1814_CR90","first-page":"154","volume":"18","author":"M Foroughipour","year":"2019","unstructured":"Foroughipour M, Gazeran S. Effectiveness and side effects of dimethyl fumarate in multiple sclerosis after 12 months of follow-up: an Iranian clinical trial. Iran J Neurol. 2019;18:154\u20138.","journal-title":"Iran J Neurol"},{"key":"1814_CR91","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jneuroim.2012.03.011","volume":"247","author":"Y Gan","year":"2012","unstructured":"Gan Y, Liu R, Wu W, Bomprezzi R, Shi FD. Antibody to alpha4 integrin suppresses natural killer cells infiltration in central nervous system in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2012;247:9\u201315.","journal-title":"J Neuroimmunol"},{"key":"1814_CR92","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s13311-020-00848-z","volume":"17","author":"SR Dunham","year":"2020","unstructured":"Dunham SR, Schmidt R, Clifford DB. Treatment of progressive multifocal leukoencephalopathy using immune restoration. Neurotherapeutics. 2020;17:955\u201365.","journal-title":"Neurotherapeutics"},{"key":"1814_CR93","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s40265-024-02011-w","volume":"84","author":"AK Carlson","year":"2024","unstructured":"Carlson AK, Amin M, Cohen JA. Drugs targeting CD20 in multiple sclerosis: pharmacology, efficacy, safety, and tolerability. Drugs. 2024;84:285\u2013304.","journal-title":"Drugs"},{"key":"1814_CR94","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.102787","volume":"49","author":"KR Cotchett","year":"2021","unstructured":"Cotchett KR, Dittel BN, Obeidat AZ. Comparison of the efficacy and safety of anti-CD20 B-cell depleting drugs in multiple sclerosis. Mult Scler Relat Disord. 2021;49:102787.","journal-title":"Mult Scler Relat Disord"},{"key":"1814_CR95","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/cei.13208","volume":"194","author":"Z Li","year":"2018","unstructured":"Li Z, Richards S, Surks HK, Jacobs A, Panzara MA. Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis. Clin Exp Immunol. 2018;194:295\u2013314.","journal-title":"Clin Exp Immunol"},{"key":"1814_CR96","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1177\/2040622313479137","volume":"4","author":"O Kousin-Ezewu","year":"2013","unstructured":"Kousin-Ezewu O, Coles A. Alemtuzumab in multiple sclerosis: latest evidence and clinical prospects. Ther Adv Chronic Dis. 2013;4:97\u2013103.","journal-title":"Ther Adv Chronic Dis"},{"key":"1814_CR97","first-page":"s343","volume":"19","author":"B Weinstock-Guttman","year":"2013","unstructured":"Weinstock-Guttman B. An update on new and emerging therapies for relapsing-remitting multiple sclerosis. Am J Manag Care. 2013;19:s343\u201354.","journal-title":"Am J Manag Care"},{"key":"1814_CR98","doi-asserted-by":"crossref","unstructured":"Reidy M, Khan M, Mills EA, Wu Q, Garton J, Draayer DE, et al. New frontiers in multiple sclerosis treatment: from targeting costimulatory molecules to bispecific antibodies. Int J Mol Sci. 2025;26:3880.","DOI":"10.3390\/ijms26083880"},{"key":"1814_CR99","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.953649","volume":"13","author":"A Mariottini","year":"2022","unstructured":"Mariottini A, Muraro PA, Lunemann JD. Antibody-mediated cell depletion therapies in multiple sclerosis. Front Immunol. 2022;13:953649.","journal-title":"Front Immunol"},{"key":"1814_CR100","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s13311-022-01224-9","volume":"19","author":"N Krajnc","year":"2022","unstructured":"Krajnc N, Bsteh G, Berger T, Mares J, Hartung HP. Monoclonal antibodies in the treatment of relapsing multiple sclerosis: an overview with emphasis on pregnancy, vaccination, and risk management. Neurotherapeutics. 2022;19:753\u201373.","journal-title":"Neurotherapeutics"},{"key":"1814_CR101","doi-asserted-by":"crossref","unstructured":"Rodi M, de Lastic AL, Panagoulias I, Aggeletopoulou I, Kelaidonis K, Matsoukas J, et al. Myelin oligodendrocyte glycoprotein (MOG)35-55 mannan conjugate induces human T-cell tolerance and can be used as a personalized therapy for multiple sclerosis. Int J Mol Sci. 2024;25:6092.","DOI":"10.3390\/ijms25116092"},{"key":"1814_CR102","doi-asserted-by":"publisher","first-page":"e0320814","DOI":"10.1371\/journal.pone.0320814","volume":"20","author":"HK Ozturk","year":"2025","unstructured":"Ozturk HK, Slanar O, Michalickova D. Safety and efficacy of antigen-specific therapeutic approaches for multiple sclerosis: systematic review. PLoS One. 2025;20:e0320814.","journal-title":"PLoS One"},{"key":"1814_CR103","doi-asserted-by":"publisher","first-page":"8463","DOI":"10.1073\/pnas.1820039116","volume":"116","author":"I Zubizarreta","year":"2019","unstructured":"Zubizarreta I, Florez-Grau G, Vila G, Cabezon R, Espa\u00f1a C, Andorra M, et al. Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial. Proc Natl Acad Sci USA. 2019;116:8463\u201370.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1814_CR104","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1021\/nn405033r","volume":"8","author":"Z Hunter","year":"2014","unstructured":"Hunter Z, McCarthy DP, Yap WT, Harp CT, Getts DR, Shea LD, et al. A biodegradable nanoparticle platform for the induction of antigen-specific immune tolerance for treatment of autoimmune disease. ACS Nano. 2014;8:2148\u201360.","journal-title":"ACS Nano"},{"key":"1814_CR105","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41565-020-00810-2","volume":"16","author":"A Cifuentes-Rius","year":"2021","unstructured":"Cifuentes-Rius A, Desai A, Yuen D, Johnston APR, Voelcker NH. Inducing immune tolerance with dendritic cell-targeting nanomedicines. Nat Nanotechnol. 2021;16:37\u201346.","journal-title":"Nat Nanotechnol"},{"key":"1814_CR106","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1039\/D2BM00444E","volume":"10","author":"H Wang","year":"2022","unstructured":"Wang H, Shang J, He Z, Zheng M, Jia H, Zhang Y, et al. Dual peptide nanoparticle platform for enhanced antigen-specific immune tolerance for the treatment of experimental autoimmune encephalomyelitis. Biomater Sci. 2022;10:3878\u201391.","journal-title":"Biomater Sci"},{"key":"1814_CR107","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122997","volume":"316","author":"NM Phan","year":"2025","unstructured":"Phan NM, Nguyen TL, Min DK, Kim J. Mesoporous polydopamine nanoparticle-based tolerogenic vaccine induces antigen-specific immune tolerance to prevent and treat autoimmune multiple sclerosis. Biomaterials. 2025;316:122997.","journal-title":"Biomaterials"},{"key":"1814_CR108","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1016\/j.ymthe.2017.03.032","volume":"25","author":"R Kuo","year":"2017","unstructured":"Kuo R, Saito E, Miller SD, Shea LD. Peptide-conjugated nanoparticles reduce positive co-stimulatory expression and T cell activity to induce tolerance. Mol Ther. 2017;25:1676\u201385.","journal-title":"Mol Ther"},{"key":"1814_CR109","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.3389\/fimmu.2018.01169","volume":"9","author":"G Florez-Grau","year":"2018","unstructured":"Florez-Grau G, Zubizarreta I, Cabezon R, Villoslada P, Benitez-Ribas D. Tolerogenic dendritic cells as a promising antigen-specific therapy in the treatment of multiple sclerosis and neuromyelitis optica from preclinical to clinical trials. Front Immunol. 2018;9:1169.","journal-title":"Front Immunol"},{"key":"1814_CR110","doi-asserted-by":"publisher","first-page":"e030309","DOI":"10.1136\/bmjopen-2019-030309","volume":"9","author":"B Willekens","year":"2019","unstructured":"Willekens B, Presas-Rodr\u00edguez S, Mansilla MJ, Derdelinckx J, Lee WP, Nijs G, et al. Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration. BMJ Open. 2019;9:e030309.","journal-title":"BMJ Open"},{"key":"1814_CR111","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2023.103051","volume":"138","author":"L Passeri","year":"2023","unstructured":"Passeri L, Andolfi G, Bassi V, Russo F, Giacomini G, Laudisa C, et al. Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell-mediated diseases. J Autoimmun. 2023;138:103051.","journal-title":"J Autoimmun"},{"key":"1814_CR112","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60082-z","volume":"16","author":"J Robert","year":"2025","unstructured":"Robert J, Feuillolay M, de Temple-Llavero M, Akossi RF, Mhanna V, Cherai M, et al. Expression of an interleukin-2 partial agonist enhances regulatory T cell persistence and efficacy in mouse autoimmune models. Nat Commun. 2025;16:4891.","journal-title":"Nat Commun"},{"key":"1814_CR113","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.661875","volume":"12","author":"C Selck","year":"2021","unstructured":"Selck C, Dominguez-Villar M. Antigen-specific regulatory T cell therapy in autoimmune diseases and transplantation. Front Immunol. 2021;12:661875.","journal-title":"Front Immunol"},{"key":"1814_CR114","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nrd.2018.148","volume":"17","author":"A Sharabi","year":"2018","unstructured":"Sharabi A, Tsokos MG, Ding Y, Malek TR, Klatzmann D, Tsokos GC. Regulatory T cells in the treatment of disease. Nat Rev Drug Discov. 2018;17:823\u201344.","journal-title":"Nat Rev Drug Discov"},{"key":"1814_CR115","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-56739-2","volume":"14","author":"TT Yang","year":"2024","unstructured":"Yang TT, Liu PJ, Sun QY, Wang ZY, Yuan GB, Fan ZX, et al. CD4+CD25+ regulatory T cells ex vivo generated from autologous naive CD4+ T cells suppress EAE progression. Sci Rep. 2024;14:6262.","journal-title":"Sci Rep"},{"key":"1814_CR116","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62628-7","volume":"16","author":"H Cheng","year":"2025","unstructured":"Cheng H, Nan F, Ji N, Ma X, Zhang J, Liang H, et al. Regulatory T cell therapy promotes TGF-beta and IL-6-dependent pro-inflammatory Th17 cell generation by reducing IL-2. Nat Commun. 2025;16:7644.","journal-title":"Nat Commun"},{"key":"1814_CR117","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41573-019-0041-4","volume":"18","author":"LMR Ferreira","year":"2019","unstructured":"Ferreira LMR, Muller YD, Bluestone JA, Tang Q. Next-generation regulatory T cell therapy. Nat Rev Drug Discov. 2019;18:749\u201369.","journal-title":"Nat Rev Drug Discov"},{"key":"1814_CR118","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.ymthe.2017.09.001","volume":"26","author":"GD Keeler","year":"2018","unstructured":"Keeler GD, Kumar S, Palaschak B, Silverberg EL, Markusic DM, Jones NT, et al. Gene therapy-induced antigen-specific Tregs inhibit neuroinflammation and reverse disease in a mouse model of multiple sclerosis. Mol Ther. 2018;26:173\u201383.","journal-title":"Mol Ther"},{"key":"1814_CR119","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2020.104222","volume":"358","author":"A De Paula Pohl","year":"2020","unstructured":"De Paula Pohl A, Schmidt A, Zhang AH, Maldonado T, Konigs C, Scott DW. Engineered regulatory T cells expressing myelin-specific chimeric antigen receptors suppress EAE progression. Cell Immunol. 2020;358:104222.","journal-title":"Cell Immunol"},{"key":"1814_CR120","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.3389\/fimmu.2018.02359","volume":"9","author":"Q Zhang","year":"2018","unstructured":"Zhang Q, Lu W, Liang CL, Chen Y, Liu H, Qiu F, et al. Chimeric antigen receptor (CAR) Treg: a promising approach to inducing immunological tolerance. Front Immunol. 2018;9:2359.","journal-title":"Front Immunol"},{"key":"1814_CR121","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.934343","volume":"13","author":"T Riet","year":"2022","unstructured":"Riet T, Chmielewski M. Regulatory CAR-T cells in autoimmune diseases: progress and current challenges. Front Immunol. 2022;13:934343.","journal-title":"Front Immunol"},{"key":"1814_CR122","doi-asserted-by":"publisher","first-page":"6526","DOI":"10.1007\/s00415-024-12642-4","volume":"271","author":"AM Konitsioti","year":"2024","unstructured":"Konitsioti AM, Pruss H, Laurent S, Fink GR, Heesen C, Warnke C. Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review. J Neurol. 2024;271:6526\u201342.","journal-title":"J Neurol"},{"key":"1814_CR123","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03262-w","volume":"21","author":"J Frikeche","year":"2024","unstructured":"Frikeche J, David M, Mouska X, Treguer D, Cui Y, Rouquier S, et al. MOG-specific CAR Tregs: a novel approach to treat multiple sclerosis. J Neuroinflammation. 2024;21:268.","journal-title":"J Neuroinflammation"},{"key":"1814_CR124","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8860813","volume":"2020","author":"MJ Tavassolifar","year":"2020","unstructured":"Tavassolifar MJ, Moghadasi AN, Esmaeili B, Sadatpour O, Vodjgani M, Izad M. Redox imbalance in CD4+ T cells of relapsing-remitting multiple sclerosis patients. Oxid Med Cell Longev. 2020;2020:8860813.","journal-title":"Oxid Med Cell Longev"},{"key":"1814_CR125","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fncel.2018.00114","volume":"12","author":"H Solleiro-Villavicencio","year":"2018","unstructured":"Solleiro-Villavicencio H, Rivas-Arancibia S. Effect of chronic oxidative stress on neuroinflammatory response mediated by CD4+\u00a0T cells in neurodegenerative diseases. Front Cell Neurosci. 2018;12:114.","journal-title":"Front Cell Neurosci"},{"key":"1814_CR126","doi-asserted-by":"crossref","unstructured":"Rubino V, Palatucci AT, La Rosa G, Giovazzino A, Aruta F, Damiano S, et al. Superoxide dismutase-1 intracellular content in T lymphocytes associates with increased regulatory T cell level in multiple sclerosis subjects undergoing immune-modulating treatment. Antioxidants (Basel). 2021;10:1940.","DOI":"10.3390\/antiox10121940"},{"key":"1814_CR127","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.bbi.2017.02.018","volume":"62","author":"S Neil","year":"2017","unstructured":"Neil S, Huh J, Baronas V, Li X, McFarland HF, Cherukuri M, et al. Oral administration of the nitroxide radical TEMPOL exhibits immunomodulatory and therapeutic properties in multiple sclerosis models. Brain Behav Immun. 2017;62:332\u201343.","journal-title":"Brain Behav Immun"},{"key":"1814_CR128","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.703972","volume":"12","author":"MD Chavez","year":"2021","unstructured":"Chavez MD, Tse HM. Targeting mitochondrial-derived reactive oxygen species in T cell-mediated autoimmune diseases. Front Immunol. 2021;12:703972.","journal-title":"Front Immunol"},{"key":"1814_CR129","doi-asserted-by":"publisher","first-page":"24696","DOI":"10.1021\/acsnano.3c04497","volume":"17","author":"NM Phan","year":"2023","unstructured":"Phan NM, Nguyen TL, Shin H, Trinh TA, Kim J. ROS-scavenging lignin-based tolerogenic nanoparticle vaccine for treatment of multiple sclerosis. ACS Nano. 2023;17:24696\u2013709.","journal-title":"ACS Nano"},{"key":"1814_CR130","doi-asserted-by":"publisher","first-page":"33106","DOI":"10.1021\/acsami.4c05428","volume":"16","author":"TL Nguyen","year":"2024","unstructured":"Nguyen TL, Phan NM, Kim J. Administration of ROS-scavenging cerium oxide nanoparticles simply mixed with autoantigenic peptides induces antigen-specific immune tolerance against autoimmune encephalomyelitis. ACS Appl Mater Interfaces. 2024;16:33106\u201320.","journal-title":"ACS Appl Mater Interfaces"},{"key":"1814_CR131","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7191080","volume":"2020","author":"V Pegoretti","year":"2020","unstructured":"Pegoretti V, Swanson KA, Bethea JR, Probert L, Eisel ULM, Fischer R. Inflammation and oxidative stress in multiple sclerosis: consequences for therapy development. Oxid Med Cell Longev. 2020;2020:7191080.","journal-title":"Oxid Med Cell Longev"},{"key":"1814_CR132","doi-asserted-by":"crossref","unstructured":"Zha Z, Liu S, Liu Y, Li C, Wang L. Potential utility of natural products against oxidative stress in animal models of multiple sclerosis. Antioxidants (Basel). 2022;11:1495.","DOI":"10.3390\/antiox11081495"},{"key":"1814_CR133","doi-asserted-by":"crossref","unstructured":"Theodosis-Nobelos P, Rekka EA. The multiple sclerosis modulatory potential of natural multi-targeting antioxidants. Molecules. 2022;27:8402.","DOI":"10.3390\/molecules27238402"},{"key":"1814_CR134","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1604987","volume":"16","author":"X Sun","year":"2025","unstructured":"Sun X, Zhang F, Wang L, Lee G, Yang S, Zhou D, et al. Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights into crosstalk between immune niches and CNS. Front Immunol. 2025;16:1604987.","journal-title":"Front Immunol"},{"key":"1814_CR135","doi-asserted-by":"crossref","unstructured":"Klotz L, Eschborn M, Lindner M, Liebmann M, Herold M, Janoschka C, et al. Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects. Sci Transl Med. 2019;11:eaao5563.","DOI":"10.1126\/scitranslmed.aao5563"},{"key":"1814_CR136","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2025.106319","volume":"95","author":"S Zhai","year":"2025","unstructured":"Zhai S, Chen Y, Jiang T, Wu F, Cheng X, Wang Q, et al. Traditional Chinese medicine provides candidates for multiple sclerosis: a review based on the progress of MS and potent treatment medicine. Mult Scler Relat Disord. 2025;95:106319.","journal-title":"Mult Scler Relat Disord"},{"key":"1814_CR137","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155248","volume":"123","author":"J Yuan","year":"2024","unstructured":"Yuan J, Tao Y, Wang M, Huang F, Wu X. Natural compounds as potential therapeutic candidates for multiple sclerosis: emerging preclinical evidence. Phytomedicine. 2024;123:155248.","journal-title":"Phytomedicine"},{"key":"1814_CR138","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151790","volume":"763","author":"J Xie","year":"2025","unstructured":"Xie J, Wu M, Li L, Zhu L, Hu L, Li Y, et al. Integrated bioinformatics and experimental verification to dissect the mechanisms and bioactive ingredients of Radix Rehmanniae in treating multiple sclerosis. Biochem Biophys Res Commun. 2025;763:151790.","journal-title":"Biochem Biophys Res Commun"},{"key":"1814_CR139","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1429895","volume":"15","author":"JY Wu","year":"2024","unstructured":"Wu JY, Yang JL, Hu JL, Xu S, Zhang XJ, Qian SY, et al. Reporting quality and risk of bias of randomized controlled trials of Chinese herbal medicine for multiple sclerosis. Front Immunol. 2024;15:1429895.","journal-title":"Front Immunol"},{"key":"1814_CR140","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1449101","volume":"15","author":"Y Shi","year":"2024","unstructured":"Shi Y, Ma P. Pharmacological effects of Astragalus polysaccharides in treating neurodegenerative diseases. Front Pharmacol. 2024;15:1449101.","journal-title":"Front Pharmacol"},{"key":"1814_CR141","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114820","volume":"285","author":"M Li","year":"2022","unstructured":"Li M, Jiang H, Hao Y, Du K, Du H, Ma C, et al. A systematic review on botany, processing, application, phytochemistry and pharmacological action of Radix Rehmanniae. J Ethnopharmacol. 2022;285:114820.","journal-title":"J Ethnopharmacol"},{"key":"1814_CR142","first-page":"81","volume":"20","author":"SH Kim","year":"2017","unstructured":"Kim SH, Yook TH, Kim JU. Rehmanniae radix, an effective treatment for patients with various inflammatory and metabolic diseases: results from a review of Korean publications. J Pharmacopunct. 2017;20:81\u20138.","journal-title":"J Pharmacopunct"},{"key":"1814_CR143","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/j.ijbiomac.2018.09.187","volume":"120","author":"M Kwak","year":"2018","unstructured":"Kwak M, Yu K, Lee PC, Jin JO. Rehmannia glutinosa polysaccharide functions as a mucosal adjuvant to induce dendritic cell activation in mediastinal lymph node. Int J Biol Macromol. 2018;120:1618\u201323.","journal-title":"Int J Biol Macromol"},{"key":"1814_CR144","doi-asserted-by":"publisher","first-page":"864","DOI":"10.3389\/fphys.2018.00864","volume":"9","author":"W Li","year":"2018","unstructured":"Li W, Wu H, Gao C, Yang D, Yang D, Shen J. Radix Rehmanniae extract ameliorates experimental autoimmune encephalomyelitis by suppressing macrophage-derived nitrative damage. Front Physiol. 2018;9:864.","journal-title":"Front Physiol"},{"key":"1814_CR145","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1089\/jmf.2011.1940","volume":"15","author":"Y Han","year":"2012","unstructured":"Han Y, Jung HW, Lee JY, Kim JS, Kang SS, Kim YS, et al. 2,5-dihydroxyacetophenone isolated from Rehmanniae radix preparata inhibits inflammatory responses in lipopolysaccharide-stimulated RAW264.7 macrophages. J Med Food. 2012;15:505\u201310.","journal-title":"J Med Food"},{"key":"1814_CR146","first-page":"82","volume":"09","author":"Y Wang","year":"2012","unstructured":"Wang Y, X Y, Chen X. Clinical observation of the effect of Dihuang Yinzi combined with Western medicine in preventing relapses of multiple sclerosis. J Sichuan Tradit Chin Med. 2012;09:82\u201383.","journal-title":"J Sichuan Tradit Chin Med"},{"key":"1814_CR147","first-page":"16","volume":"6","author":"M Gao","year":"2008","unstructured":"Gao M, Lin M, Zhang K, Lin Y, Lv N. Clinical observation on 38 cases of acute recurrent multiple sclerosis treated with dihuangheji (Capsule). Hunan J Tradit Chin Med. 2008;6:16\u20137.","journal-title":"Hunan J Tradit Chin Med"},{"key":"1814_CR148","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1635833","volume":"16","author":"X Guan","year":"2025","unstructured":"Guan X, Wu Y, Jia Q, Zheng Y, Zou M, Liu J, et al. Efficacy and safety of Chinese herbal medicine for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol. 2025;16:1635833.","journal-title":"Front Pharmacol"},{"key":"1814_CR149","first-page":"4220","volume":"09","author":"Y Fan","year":"2018","unstructured":"Fan Y, C K, You Y, Wang S, Yang T, Wan J. Clinical efficacy observation of Bushen Yisui capsule on relapsing remitting multiple sclerosis with syndrome of deficiency of kidney-liver yin. Chin J Tradit Chin Med. 2018;09:4220\u20133.","journal-title":"Chin J Tradit Chin Med"},{"key":"1814_CR150","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ctim.2017.02.004","volume":"31","author":"L Song","year":"2017","unstructured":"Song L, Zhou QH, Wang HL, Liao FJ, Hua L, Zhang HF, et al. Chinese herbal medicine adjunct therapy in patients with acute relapse of multiple sclerosis: a systematic review and meta-analysis. Complement Ther Med. 2017;31:71\u201381.","journal-title":"Complement Ther Med"},{"key":"1814_CR151","first-page":"809","volume":"39","author":"M Wei","year":"2019","unstructured":"Wei M, Yang T, Li Q, Zhou D, Du Z, Fan Y. Protective effects of catalpol and rhein in murine experimental autoimmune encephalomyelitis via regulation of T helper (Th) 1, Th2, Th17, and regulatory T cell responses. J Tradit Chin Med. 2019;39:809\u201317.","journal-title":"J Tradit Chin Med"},{"key":"1814_CR152","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3349\/ymj.2022.63.1.56","volume":"63","author":"Y Di","year":"2022","unstructured":"Di Y, Zhang M, Chen Y, Sun R, Shen M, Tian F, et al. Catalpol inhibits Tregs-to-Th17 cell transdifferentiation by up-regulating Let-7g-5p to reduce STAT3 protein levels. Yonsei Med J. 2022;63:56\u201365.","journal-title":"Yonsei Med J"},{"key":"1814_CR153","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.628209","volume":"12","author":"Y Sun","year":"2021","unstructured":"Sun Y, Ji J, Zha Z, Zhao H, Xue B, Jin L, et al. Effect and mechanism of Catalpol on remyelination via regulation of the Notch1 signaling pathway. Front Pharmacol. 2021;12:628209.","journal-title":"Front Pharmacol"},{"key":"1814_CR154","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.lfs.2006.09.010","volume":"80","author":"YY Tian","year":"2006","unstructured":"Tian YY, An LJ, Jiang L, Duan YL, Chen J, Jiang B. Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures. Life Sci. 2006;80:193\u20139.","journal-title":"Life Sci"},{"key":"1814_CR155","doi-asserted-by":"crossref","unstructured":"Dai XX, Su SL, Cai HD, Wei DD, Zheng TY, Zhu ZH, et al. Comparative pharmacokinetics of acteoside from total glycoside extracted from leaves of Rehmannia and Dihuangye total glycoside capsule in normal and diabetic nephropathy rats. Biomed Chromatogr. 2017;31:10.1002\/bmc.4013.","DOI":"10.1002\/bmc.4013"},{"key":"1814_CR156","doi-asserted-by":"crossref","unstructured":"Marcetic M, Bufan B, Drobac M, Antic Stankovic J, Arsenovic Ranin N, Milenkovic MT, et al. Multifaceted biological properties of verbascoside\/acteoside: antimicrobial, cytotoxic, anti-inflammatory, and immunomodulatory effects. Antibiotics (Basel). 2025;14:697.","DOI":"10.3390\/antibiotics14070697"},{"key":"1814_CR157","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1002\/JLB.3MA0422-510R","volume":"112","author":"M Wu","year":"2022","unstructured":"Wu M, Yu S, Chen Y, Meng W, Chen H, He J, et al. Acteoside promotes B cell-derived IL-10 production and ameliorates autoimmunity. J Leukoc Biol. 2022;112:875\u201385.","journal-title":"J Leukoc Biol"},{"key":"1814_CR158","first-page":"9","volume":"10","author":"H Zeng","year":"2009","unstructured":"Zeng H, Zhang M, Zhang G, Zi X. A clinical effect observation on the buyang huanwu decoction with hormone treatment for multiple sclerosis. Pr Clin Med. 2009;10:9\u201314.","journal-title":"Pr Clin Med"},{"key":"1814_CR159","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1142\/S0192415X23500568","volume":"51","author":"XY Han","year":"2023","unstructured":"Han XY, Xu N, Yuan JF, Wu H, Shi HL, Yang L, et al. Total flavonoids of astragalus inhibit activated CD4[Formula: see text] T cells and regulate differentiation of Th17\/Th1\/Treg cells in experimental autoimmune encephalomyelitis mice by JAK\/STAT and NF[Formula: see text]B signaling pathways. Am J Chin Med. 2023;51:1233\u201348.","journal-title":"Am J Chin Med"},{"key":"1814_CR160","doi-asserted-by":"publisher","first-page":"5525","DOI":"10.1002\/jcp.29452","volume":"235","author":"N Dong","year":"2020","unstructured":"Dong N, Li X, Xue C, Zhang L, Wang C, Xu X, et al. Astragalus polysaccharides alleviate LPS-induced inflammation via the NF-kappaB\/MAPK signaling pathway. J Cell Physiol. 2020;235:5525\u201340.","journal-title":"J Cell Physiol"},{"key":"1814_CR161","doi-asserted-by":"publisher","first-page":"135","DOI":"10.12659\/MSM.912213","volume":"25","author":"G Zhang","year":"2019","unstructured":"Zhang G, Fang H, Li Y, Xu J, Zhang D, Sun Y, et al. Neuroprotective effect of astragalus polysaccharin on streptozotocin (STZ)-induced diabetic rats. Med Sci Monit. 2019;25:135\u201341.","journal-title":"Med Sci Monit"},{"key":"1814_CR162","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111303","volume":"126","author":"Y Zhao","year":"2024","unstructured":"Zhao Y, Ma J, Ding G, Wang Y, Yu H, Cheng X. Astragalus polysaccharides promote neural stem cells-derived oligodendrogenesis through attenuating CD8+ T cell infiltration in experimental autoimmune encephalomyelitis. Int Immunopharmacol. 2024;126:111303.","journal-title":"Int Immunopharmacol"},{"key":"1814_CR163","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jneuroim.2019.03.019","volume":"332","author":"Y Sun","year":"2019","unstructured":"Sun Y, Jing Y, Huang M, Ma J, Peng X, Wang J, et al. The PD-1\/PD-Ls pathway is up-regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides. J Neuroimmunol. 2019;332:78\u201390.","journal-title":"J Neuroimmunol"},{"key":"1814_CR164","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2024.111171","volume":"220","author":"J Ma","year":"2025","unstructured":"Ma J, Liu X, Zhao Y, Lu Q, Ding G, Wang Y, et al. Th17\/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis. Brain Res Bull. 2025;220:111171.","journal-title":"Brain Res Bull"},{"key":"1814_CR165","doi-asserted-by":"crossref","unstructured":"Yang F, Wen H, Ma S, Chang Q, Pan R, Liu X, et al. Icaritin promotes myelination by simultaneously enhancing the proliferation and differentiation of oligodendrocyte precursor cells. Molecules. 2023;28:5837.","DOI":"10.3390\/molecules28155837"},{"key":"1814_CR166","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/cbdd.13765","volume":"97","author":"Y Xu","year":"2021","unstructured":"Xu Y, Lu X, Zhang L, Wang L, Zhang G, Yao J, et al. Icaritin activates Nrf2\/Keap1 signaling to protect neuronal cells from oxidative stress. Chem Biol Drug Des. 2021;97:111\u201320.","journal-title":"Chem Biol Drug Des"},{"key":"1814_CR167","unstructured":"Wang LX, Li QY, Hong MF, Peng ZX, Yu QY, Wei ZS. Effects of icariin on expression of PBMC ER and GR mRNA in multiple sclerosis. J Guangdong Pharm Univ. 2017;33:265\u201369."},{"key":"1814_CR168","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3390\/molecules21010051","volume":"21","author":"H Pang","year":"2016","unstructured":"Pang H, Wu L, Tang Y, Zhou G, Qu C, Duan JA. Chemical analysis of the herbal medicine salviae miltiorrhizae radix et rhizoma (Danshen). Molecules. 2016;21:51.","journal-title":"Molecules"},{"key":"1814_CR169","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1055\/s-0035-1546196","volume":"81","author":"L Bonaccini","year":"2015","unstructured":"Bonaccini L, Karioti A, Bergonzi MC, Bilia AR. Effects of Salvia miltiorrhiza on CNS neuronal injury and degeneration: a plausible complementary role of tanshinones and depsides. Planta Med. 2015;81:1003\u201316.","journal-title":"Planta Med"},{"key":"1814_CR170","first-page":"20","volume":"19","author":"X Pan","year":"2008","unstructured":"Pan X, Chen C. Clinical observation of hyperbaric oxygen and Chinese traditional medicine in the treatment of multiple sclerosis. Hainan Med J. 2008;19:20\u20131.","journal-title":"Hainan Med J"},{"key":"1814_CR171","first-page":"278","volume":"42","author":"B Wang","year":"2019","unstructured":"Wang B, Zhao L, Duan R, Zhang M. Effect of salvianolic acids for injection on acute multiple sclerosis and serum matrix metalloproteinase-9 level. Drug Eval Res. 2019;42:278\u201382.","journal-title":"Drug Eval Res"},{"key":"1814_CR172","doi-asserted-by":"publisher","first-page":"3825","DOI":"10.1002\/ptr.8222","volume":"38","author":"T Wang","year":"2024","unstructured":"Wang T, Wang J, Xu H, Yan H, Liu Y, Zhang N, et al. Salvianolic acid B alleviates autoimmunity in Treg-deficient mice via inhibiting IL2-STAT5 signaling. Phytother Res. 2024;38:3825\u201336.","journal-title":"Phytother Res"},{"key":"1814_CR173","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.3892\/mmr.2016.5431","volume":"14","author":"J Yan","year":"2016","unstructured":"Yan J, Yang X, Han D, Feng J. Tanshinone IIA attenuates experimental autoimmune encephalomyelitis in rats. Mol Med Rep. 2016;14:1601\u20139.","journal-title":"Mol Med Rep"},{"key":"1814_CR174","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.946030","volume":"13","author":"J Wang","year":"2022","unstructured":"Wang J, Chen S, Zhang J, Wu J. Scutellaria baicalensis Georgi is a promising candidate for the treatment of autoimmune diseases. Front Pharmcol. 2022;13:946030.","journal-title":"Front Pharmcol"},{"key":"1814_CR175","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107725","volume":"96","author":"X Wang","year":"2021","unstructured":"Wang X, Yu JY, Sun Y, Wang H, Shan H, Wang S. Baicalin protects LPS-induced blood-brain barrier damage and activates Nrf2-mediated antioxidant stress pathway. Int Immunopharmacol. 2021;96:107725.","journal-title":"Int Immunopharmacol"},{"key":"1814_CR176","doi-asserted-by":"crossref","unstructured":"Liang J, Zhou Y, Cheng X, Chen J, Cao H, Guo X, et al. Baicalin attenuates H(2)O(2)-induced oxidative stress by regulating the AMPK\/Nrf2 signaling pathway in IPEC-J2 cells. Int J Mol Sci. 2023;24:9435.","DOI":"10.3390\/ijms24119435"},{"key":"1814_CR177","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s10787-025-01698-x","volume":"33","author":"OK Kuwar","year":"2025","unstructured":"Kuwar OK, Kalia N. Anti-inflammatory and antioxidant effects of baicalein: targeting Nrf2, and NFkB in neurodegenerative disease. Inflammopharmacology. 2025;33:1303\u201310.","journal-title":"Inflammopharmacology"},{"key":"1814_CR178","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.phrs.2015.08.021","volume":"100","author":"MR de Oliveira","year":"2015","unstructured":"de Oliveira MR, Nabavi SF, Habtemariam S, Erdogan Orhan I, Daglia M, Nabavi SM. The effects of baicalein and baicalin on mitochondrial function and dynamics: a review. Pharm Res. 2015;100:296\u2013308.","journal-title":"Pharm Res"},{"key":"1814_CR179","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109562","volume":"114","author":"S Ying","year":"2023","unstructured":"Ying S, Yang H, Gu Q, Wu Z, Zou N, Wang CZ, et al. The Small-molecule compound baicalein alleviates experimental autoimmune encephalomyelitis by suppressing pathogenetic CXCR6+ CD4 cells. Int Immunopharmacol. 2023;114:109562.","journal-title":"Int Immunopharmacol"},{"key":"1814_CR180","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1590\/S0100-879X2006005000115","volume":"40","author":"Y Zeng","year":"2007","unstructured":"Zeng Y, Song C, Ding X, Ji X, Yi L, Zhu K. Baicalin reduces the severity of experimental autoimmune encephalomyelitis. Braz J Med Biol Res. 2007;40:1003\u201310.","journal-title":"Braz J Med Biol Res"},{"key":"1814_CR181","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1021\/acschemneuro.9b00640","volume":"11","author":"YN Paudel","year":"2020","unstructured":"Paudel YN, Angelopoulou E, Semple B, Piperi C, Othman I, Shaikh MF. Potential neuroprotective effect of the HMGB1 inhibitor glycyrrhizin in neurological disorders. ACS Chem Neurosci. 2020;11:485\u2013500.","journal-title":"ACS Chem Neurosci"},{"key":"1814_CR182","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.yexcr.2018.05.012","volume":"369","author":"X Sun","year":"2018","unstructured":"Sun X, Zeng H, Wang Q, Yu Q, Wu J, Feng Y, et al. Glycyrrhizin ameliorates inflammatory pain by inhibiting microglial activation-mediated inflammatory response via blockage of the HMGB1-TLR4-NF-kB pathway. Exp Cell Res. 2018;369:112\u20139.","journal-title":"Exp Cell Res"},{"key":"1814_CR183","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114294","volume":"150","author":"Q Sun","year":"2025","unstructured":"Sun Q, Li L, Li J, Li SY, Zhang Y, Chen XS, et al. Glycyrrhizin alleviates brain injury in necrotizing enterocolitis model mice by suppressing HMGB1\/TLR4 pathway. Int Immunopharmacol. 2025;150:114294.","journal-title":"Int Immunopharmacol"},{"key":"1814_CR184","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117188","volume":"178","author":"YL Zhang","year":"2024","unstructured":"Zhang YL, Qu Y, Song HH, Cheng G, Lu F, Cui TT, et al. Isoliquiritigenin alleviates experimental autoimmune encephalomyelitis by modulating inflammatory and neuroprotective reactive astrocytes. Biomed Pharmacother. 2024;178:117188.","journal-title":"Biomed Pharmacother"},{"key":"1814_CR185","doi-asserted-by":"publisher","DOI":"10.1038\/srep14046","volume":"5","author":"A Guo","year":"2015","unstructured":"Guo A, He D, Xu HB, Geng CA, Zhao J. Promotion of regulatory T cell induction by immunomodulatory herbal medicine licorice and its two constituents. Sci Rep. 2015;5:14046.","journal-title":"Sci Rep"},{"key":"1814_CR186","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0955-2863(01)00215-7","volume":"13","author":"J Kanski","year":"2002","unstructured":"Kanski J, Aksenova M, Stoyanova A, Butterfield DA. Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. J Nutr Biochem. 2002;13:273\u201381.","journal-title":"J Nutr Biochem"},{"key":"1814_CR187","doi-asserted-by":"crossref","unstructured":"Liu J, Guan Y, Yang L, Fang H, Sun H, Sun Y, et al. Ferulic acid as an anti-inflammatory agent: insights into molecular mechanisms, pharmacokinetics and applications. Pharmaceuticals (Basel). 2025;18:912.","DOI":"10.3390\/ph18060912"},{"key":"1814_CR188","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1523176","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang Y, Wu L, Wang H, Jiang M, Chen Y, Zheng X, et al. Ligusticum chuanxiong: a chemical, pharmacological and clinical review. Front Pharmacol. 2025;16:1523176.","journal-title":"Front Pharmacol"},{"key":"1814_CR189","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.neuropharm.2010.12.002","volume":"60","author":"TC Or","year":"2011","unstructured":"Or TC, Yang CL, Law AH, Li JC, Lau AS. Isolation and identification of anti-inflammatory constituents from Ligusticum chuanxiong and their underlying mechanisms of action on microglia. Neuropharmacology. 2011;60:823\u201331.","journal-title":"Neuropharmacology"},{"key":"1814_CR190","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.molmed.2013.11.007","volume":"20","author":"ME Witte","year":"2014","unstructured":"Witte ME, Mahad DJ, Lassmann H, van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med. 2014;20:179\u201387.","journal-title":"Trends Mol Med"},{"key":"1814_CR191","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jneuroim.2015.05.009","volume":"284","author":"Q Huang","year":"2015","unstructured":"Huang Q, Ma X, Zhu DL, Chen L, Jiang Y, Zhou L, et al. Total glucosides of peony attenuate experimental autoimmune encephalomyelitis in C57BL\/6 mice. J Neuroimmunol. 2015;284:67\u201373.","journal-title":"J Neuroimmunol"},{"key":"1814_CR192","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114434","volume":"185","author":"CL Liang","year":"2021","unstructured":"Liang CL, Lu W, Qiu F, Li D, Liu H, Zheng F, et al. Paeoniflorin ameliorates murine lupus nephritis by increasing CD4+Foxp3+ Treg cells via enhancing mTNFalpha-TNFR2 pathway. Biochem Pharmacol. 2021;185:114434.","journal-title":"Biochem Pharmacol"},{"key":"1814_CR193","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/biof.1716","volume":"47","author":"A Memarzia","year":"2021","unstructured":"Memarzia A, Khazdair MR, Behrouz S, Gholamnezhad Z, Jafarnezhad M, Saadat S, et al. Experimental and clinical reports on anti-inflammatory, antioxidant, and immunomodulatory effects of Curcuma longa and curcumin, an updated and comprehensive review. Biofactors. 2021;47:311\u201350.","journal-title":"Biofactors"},{"key":"1814_CR194","doi-asserted-by":"crossref","unstructured":"Marcolin E, Chemello C, Piovan A, Barbierato M, Morazzoni P, Ragazzi E, et al. A combination of 5-(3\u2019,4\u2019-Dihydroxyphenyl)-gamma-valerolactone and curcumin synergistically reduces neuroinflammation in cortical microglia by targeting the NLRP3 inflammasome and the NOX2\/Nrf2 signaling pathway. Nutrients. 2025;17:1316.","DOI":"10.3390\/nu17081316"},{"key":"1814_CR195","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.jgr.2016.08.004","volume":"41","author":"JH Kim","year":"2017","unstructured":"Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. 2017;41:435\u201343.","journal-title":"J Ginseng Res"},{"key":"1814_CR196","doi-asserted-by":"crossref","unstructured":"Kim JH, Park KW, Jeong BG, Park JK, Jang HY, Oh YS, et al. Ginsenoside-enriched Panax ginseng sprouts cultivated from an aquaponic system with a novel nutrient solution regulate LPS-induced inflammatory cytokines and UVB-induced photoaging responses via MAPK\/AP-1 signaling pathways. Plants (Basel). 2025;14:1712.","DOI":"10.3390\/plants14111712"},{"key":"1814_CR197","doi-asserted-by":"crossref","unstructured":"Jang WY, Hwang JY, Cho JY. Ginsenosides from Panax ginseng as key modulators of NF-kappaB signaling are powerful anti-inflammatory and anticancer agents. Int J Mol Sci. 2023;24:6119.","DOI":"10.3390\/ijms24076119"},{"key":"1814_CR198","first-page":"751","volume":"15","author":"Q Yu","year":"2017","unstructured":"Yu Q, Zeng KW, Ma XL, Jiang Y, Tu PF, Wang XM. Ginsenoside Rk1 suppresses pro-inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells by inhibiting the Jak2\/Stat3 pathway. Chin J Nat Med. 2017;15:751\u20137.","journal-title":"Chin J Nat Med"}],"container-title":["Acta Pharmacologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01814-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01814-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01814-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:02:52Z","timestamp":1779782572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01814-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":198,"alternative-id":["1814"],"URL":"https:\/\/doi.org\/10.1038\/s41401-026-01814-9","relation":{},"ISSN":["1671-4083","1745-7254"],"issn-type":[{"value":"1671-4083","type":"print"},{"value":"1745-7254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"5 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}