{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:16:11Z","timestamp":1792800971886,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071380"],"award-info":[{"award-number":["82071380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873743"],"award-info":[{"award-number":["81873743"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801223"],"award-info":[{"award-number":["81801223"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tongji Hospital (HUST) Foundation for Excellent Young Scientist","award":["2020YQ06"],"award-info":[{"award-number":["2020YQ06"]}],"id":[{"id":"https:\/\/ror.org\/04xy45965","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>\n                      Neuromyelitis optica spectrum disorder (NMOSD) is mainly an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. Systemic and local inflammatory responses play a key role in the pathophysiology of NMOSD. However, the role of the crucial immunomodulators CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      forkhead box P3\n                      <jats:sup>+<\/jats:sup>\n                      (Foxp3) regulatory T cells (Tregs) has not been investigated in NMOSD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-five patients with anti-AQP4-postive NMOSD undergoing an attack and 21 healthy controls (HCs) were enrolled. Frequencies of T cell subsets and Tregs in the peripheral blood were assessed by flow cytometry. Additionally, a model of NMOSD using purified immunoglobulin G from anti-AQP4-antibodies-positive patients with NMOSD and human complement injected into brain of female adult C57BL\/6J mice was established. Infiltrated Tregs into NMOSD mouse brain lesions were analyzed by flow cytometry, histological sections, and real-time quantitative Polymerase Chain Reaction. Astrocyte loss, demyelination, and inflammatory response were also evaluated in our NMOSD mouse model. Finally, we examined the effects of both depletion and adoptive transfer of Tregs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The percentage of Tregs, especially na\u00efve Tregs, among total T cells in peripheral blood was significantly decreased in NMOSD patients at acute stage when compared to HCs. Within our animal model, the number and proportion of Tregs among CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were increased in the lesion of mice with NMOSD. Depletion of Tregs profoundly enhanced astrocyte loss and demyelination in these mice, while adoptive transfer of Tregs attenuated brain damage. Mechanistically, the absence of Tregs induced more macrophage infiltration, microglial activation, and T cells invasion, and modulated macrophages\/microglia toward a classical activation phenotype, releasing more chemokines and pro-inflammatory cytokines. In contrast, Tregs transfer ameliorated immune cell infiltration in NMOSD mice, including macrophages, neutrophils, and T cells, and skewed macrophages and microglia towards an alternative activation phenotype, thereby decreasing the level of chemokines and pro-inflammatory cytokines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tregs may be key immunomodulators ameliorating brain damage via dampening inflammatory response after NMOSD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-021-02266-0","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:03:25Z","timestamp":1631707405000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Regulatory T cells protect against brain damage by alleviating inflammatory response in neuromyelitis optica spectrum disorder"],"prefix":"10.1186","volume":"18","author":[{"given":"Xue","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Han","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Hui","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale B.","family":"Bosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Tao","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-0811","authenticated-orcid":false,"given":"Dai-Shi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"issue":"Pt 7","key":"2266_CR1","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1093\/brain\/awf151","volume":"125","author":"CF Lucchinetti","year":"2002","unstructured":"Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain. 2002;125(Pt 7):1450\u201361. https:\/\/doi.org\/10.1093\/brain\/awf151.","journal-title":"Brain."},{"issue":"7","key":"2266_CR2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrneurol.2010.72","volume":"6","author":"S Jarius","year":"2010","unstructured":"Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol. 2010;6(7):383\u201392. https:\/\/doi.org\/10.1038\/nrneurol.2010.72.","journal-title":"Nat Rev Neurol"},{"issue":"9451","key":"2266_CR3","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","volume":"364","author":"VA Lennon","year":"2004","unstructured":"Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106\u201312. https:\/\/doi.org\/10.1016\/S0140-6736(04)17551-X.","journal-title":"Lancet."},{"issue":"4","key":"2266_CR4","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1084\/jem.20050304","volume":"202","author":"VA Lennon","year":"2005","unstructured":"Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202(4):473\u20137. https:\/\/doi.org\/10.1084\/jem.20050304.","journal-title":"J Exp Med"},{"issue":"9","key":"2266_CR5","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1136\/jnnp-2018-317969","volume":"89","author":"K Kaneko","year":"2018","unstructured":"Kaneko K, Sato DK, Nakashima I. CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications. J Neurol Neurosurg Psychiatry. 2018;89(9):927\u201336.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"12","key":"2266_CR6","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1177\/1352458510379247","volume":"16","author":"A Uzawa","year":"2010","unstructured":"Uzawa A, Mori M, Arai K, Sato Y, Hayakawa S, Masuda S, et al. Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. Mult Scler. 2010;16(12):1443\u201352. https:\/\/doi.org\/10.1177\/1352458510379247.","journal-title":"Mult Scler"},{"issue":"1","key":"2266_CR7","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/bpa.12097","volume":"24","author":"A Uzawa","year":"2014","unstructured":"Uzawa A, Mori M, Kuwabara S. Cytokines and chemokines in neuromyelitis optica: pathogenetic and therapeutic implications. Brain Pathol. 2014;24(1):67\u201373. https:\/\/doi.org\/10.1111\/bpa.12097.","journal-title":"Brain Pathol"},{"issue":"1","key":"2266_CR8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00401-011-0824-0","volume":"122","author":"M Pohl","year":"2011","unstructured":"Pohl M, Fischer MT, Mader S, Schanda K, Kitic M, Sharma R, et al. Pathogenic T cell responses against aquaporin 4. Acta Neuropathol. 2011;122(1):21\u201334. https:\/\/doi.org\/10.1007\/s00401-011-0824-0.","journal-title":"Acta Neuropathol"},{"issue":"1-2","key":"2266_CR9","first-page":"120","volume":"253","author":"M Varrin-Doyer","year":"2012","unstructured":"Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, Nelson PA, Stroud RM, Cree BAC, et al. Aquaporin-4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. J Neuroimmunol. 2012;253(1-2):120.","journal-title":"J Neuroimmunol"},{"key":"2266_CR10","doi-asserted-by":"publisher","unstructured":"Pohl M, Kawakami N, Kitic M, Bauer J, Martins R, Fischer MT, et al. T cell-activation in neuromyelitis optica lesions plays a role in their formation. Acta Neuropathol Commun. 2013;1(1). https:\/\/doi.org\/10.1186\/2051-5960-1-85.","DOI":"10.1186\/2051-5960-1-85"},{"issue":"10","key":"2266_CR11","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1016\/j.jocn.2011.01.031","volume":"18","author":"HH Wang","year":"2011","unstructured":"Wang HH, Dai YQ, Qiu W, Lu ZQ, Peng FH, Wang YG, et al. Interleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse. J Clin Neurosci. 2011;18(10):1313\u20137. https:\/\/doi.org\/10.1016\/j.jocn.2011.01.031.","journal-title":"J Clin Neurosci"},{"issue":"8","key":"2266_CR12","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1172\/JCI134816","volume":"130","author":"T Chen","year":"2020","unstructured":"Chen T, Lennon VA, Liu YU, Bosco DB, Li Y, Yi MH, et al. Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion. J Clin Invest. 2020;130(8):4025\u201338. https:\/\/doi.org\/10.1172\/JCI134816.","journal-title":"J Clin Invest"},{"issue":"5","key":"2266_CR13","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(5):775\u201387. https:\/\/doi.org\/10.1016\/j.cell.2008.05.009.","journal-title":"Cell."},{"issue":"1","key":"2266_CR14","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","volume":"30","author":"SZ Josefowicz","year":"2012","unstructured":"Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30(1):531\u201364. https:\/\/doi.org\/10.1146\/annurev.immunol.25.022106.141623.","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"2266_CR15","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/ni1572","volume":"9","author":"QZ Tang","year":"2008","unstructured":"Tang QZ, Bluestone JA. The Foxp3(+) regulatory T cell: a jack of all trades, master of regulation. Nat Immunol. 2008;9(3):239\u201344. https:\/\/doi.org\/10.1038\/ni1572.","journal-title":"Nat Immunol"},{"issue":"4","key":"2266_CR16","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.immuni.2018.07.015","volume":"49","author":"JD Proto","year":"2018","unstructured":"Proto JD, Doran AC, Gusarova G, Yurdagul A Jr, Sozen E, Subramanian M, et al. Regulatory T cells promote macrophage efferocytosis during inflammation resolution. Immunity. 2018;49(4):666\u201377 e6. https:\/\/doi.org\/10.1016\/j.immuni.2018.07.015.","journal-title":"Immunity."},{"issue":"3","key":"2266_CR17","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1093\/brain\/awz017","volume":"142","author":"I Mexhitaj","year":"2019","unstructured":"Mexhitaj I, Nyirenda MH, Li R, O'Mahony J, Rezk A, Rozenberg A, et al. Abnormal effector and regulatory T cell subsets in paediatric-onset multiple sclerosis. Brain. 2019;142(3):617\u201332. https:\/\/doi.org\/10.1093\/brain\/awz017.","journal-title":"Brain"},{"issue":"7","key":"2266_CR18","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1084\/jem.20031579","volume":"199","author":"V Viglietta","year":"2004","unstructured":"Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004;199(7):971\u20139. https:\/\/doi.org\/10.1084\/jem.20031579.","journal-title":"J Exp Med"},{"issue":"6","key":"2266_CR19","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nm.2389","volume":"17","author":"M Dominguez-Villar","year":"2011","unstructured":"Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease. Nat Med. 2011;17(6):673\u20135. https:\/\/doi.org\/10.1038\/nm.2389.","journal-title":"Nat Med"},{"issue":"1","key":"2266_CR20","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/j.1749-6632.2012.06840.x","volume":"1274","author":"M Thiruppathi","year":"2012","unstructured":"Thiruppathi M, Rowin J, Li Jiang Q, Sheng JR, Prabhakar BS, Meriggioli MN. Functional defect in regulatory T cells in myasthenia gravis. Ann N Y Acad Sci. 2012;1274(1):68\u201376. https:\/\/doi.org\/10.1111\/j.1749-6632.2012.06840.x.","journal-title":"Ann N Y Acad Sci"},{"issue":"2","key":"2266_CR21","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1182\/blood-2003-11-3900","volume":"105","author":"A Balandina","year":"2005","unstructured":"Balandina A, Lecart S, Dartevelle P, Saoudi A, Berrih-Aknin S. Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood. 2005;105(2):735\u201341. https:\/\/doi.org\/10.1182\/blood-2003-11-3900.","journal-title":"Blood."},{"issue":"7","key":"2266_CR22","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1093\/intimm\/dxn044","volume":"20","author":"M Bonelli","year":"2008","unstructured":"Bonelli M, Savitskaya A, von Dalwigk K, Steiner CW, Aletaha D, Smolen JS, et al. Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE). Int Immunol. 2008;20(7):861\u20138. https:\/\/doi.org\/10.1093\/intimm\/dxn044.","journal-title":"Int Immunol"},{"key":"2266_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jaut.2019.02.001","volume":"99","author":"I Cammarata","year":"2019","unstructured":"Cammarata I, Martire C, Citro A, Raimondo D, Fruci D, Melaiu O, et al. Counter-regulation of regulatory T cells by autoreactive CD8(+) T cells in rheumatoid arthritis. J Autoimmun. 2019;99:81\u201397. https:\/\/doi.org\/10.1016\/j.jaut.2019.02.001.","journal-title":"J Autoimmun"},{"key":"2266_CR24","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jaut.2018.01.004","volume":"90","author":"RS Peres","year":"2018","unstructured":"Peres RS, Donate PB, Talbot J, Cecilio NT, Lobo PR, Machado CC, et al. TGF-beta signalling defect is linked to low CD39 expression on regulatory T cells and methotrexate resistance in rheumatoid arthritis. J Autoimmun. 2018;90:49\u201358. https:\/\/doi.org\/10.1016\/j.jaut.2018.01.004.","journal-title":"J Autoimmun"},{"issue":"7","key":"2266_CR25","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/s41590-018-0120-4","volume":"19","author":"M Dominguez-Villar","year":"2018","unstructured":"Dominguez-Villar M, Hafler DA. Regulatory T cells in autoimmune disease. Nat Immunol. 2018;19(7):665\u201373. https:\/\/doi.org\/10.1038\/s41590-018-0120-4.","journal-title":"Nat Immunol"},{"issue":"Pt 2","key":"2266_CR26","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1093\/brain\/awp309","volume":"133","author":"S Saadoun","year":"2010","unstructured":"Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133(Pt 2):349\u201361. https:\/\/doi.org\/10.1093\/brain\/awp309.","journal-title":"Brain"},{"issue":"3","key":"2266_CR27","doi-asserted-by":"publisher","first-page":"e561","DOI":"10.1212\/NXI.0000000000000561","volume":"6","author":"W Zhu","year":"2019","unstructured":"Zhu W, Wang Z, Hu S, Gong Y, Liu Y, Song H, et al. Human C5-specific single-chain variable fragment ameliorates brain injury in a model of NMOSD. Neurol Neuroimmunol Neuroinflamm. 2019;6(3):e561.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2266_CR28","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.bbi.2017.04.023","volume":"65","author":"Z Wang","year":"2017","unstructured":"Wang Z, Guo W, Liu YC, Gong Y, Ding XL, Shi KB, et al. Low expression of complement inhibitory protein CD59 contributes to humoral autoimmunity against astrocytes. Brain Behav Immun. 2017;65:173\u201382. https:\/\/doi.org\/10.1016\/j.bbi.2017.04.023.","journal-title":"Brain Behav Immun"},{"issue":"2","key":"2266_CR29","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/nm.1927","volume":"15","author":"A Liesz","year":"2009","unstructured":"Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S, et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med. 2009;15(2):192\u20139. https:\/\/doi.org\/10.1038\/nm.1927.","journal-title":"Nat Med"},{"issue":"28","key":"2266_CR30","doi-asserted-by":"publisher","first-page":"14290","DOI":"10.1073\/pnas.1819343116","volume":"116","author":"M Baydyuk","year":"2019","unstructured":"Baydyuk M, Cha DS, Hu J, Yamazaki R, Miller EM, Smith VN, et al. Tracking the evolution of CNS remyelinating lesion in mice with neutral red dye. Proc Natl Acad Sci U S A. 2019;116(28):14290\u20139. https:\/\/doi.org\/10.1073\/pnas.1819343116.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2266_CR31","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method. Methods. 2001;25(4):402\u20138. https:\/\/doi.org\/10.1006\/meth.2001.1262.","journal-title":"Methods."},{"issue":"49","key":"2266_CR32","doi-asserted-by":"publisher","first-page":"19446","DOI":"10.1073\/pnas.0706832104","volume":"104","author":"MM Tiemessen","year":"2007","unstructured":"Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJC, John S, Taams LS. CD4(+)CD25(+)Foxp3(+) regulatory T cells induce alternative activation of human monocytes\/macrophages. Proc Natl Acad Sci U S A. 2007;104(49):19446\u201351. https:\/\/doi.org\/10.1073\/pnas.0706832104.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2266_CR33","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.msard.2019.01.047","volume":"30","author":"L Brill","year":"2019","unstructured":"Brill L, Lavon I, Vaknin-Dembinsky A. Foxp3+ regulatory T cells expression in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord. 2019;30:114\u20138. https:\/\/doi.org\/10.1016\/j.msard.2019.01.047.","journal-title":"Mult Scler Relat Disord"},{"issue":"18","key":"2266_CR34","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1161\/CIRCULATIONAHA.118.035047","volume":"138","author":"K Shirakawa","year":"2018","unstructured":"Shirakawa K, Endo J, Kataoka M, Katsumata Y, Yoshida N, Yamamoto T, et al. IL (Interleukin)-10-STAT3-Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction. Circulation. 2018;138(18):2021\u201335. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.118.035047.","journal-title":"Circulation."},{"issue":"5","key":"2266_CR35","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.4049\/jimmunol.169.5.2253","volume":"169","author":"R Lang","year":"2002","unstructured":"Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ. Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol. 2002;169(5):2253\u201363. https:\/\/doi.org\/10.4049\/jimmunol.169.5.2253.","journal-title":"J Immunol"},{"issue":"9","key":"2266_CR36","doi-asserted-by":"publisher","first-page":"3701","DOI":"10.1073\/pnas.1017385108","volume":"108","author":"N Chihara","year":"2011","unstructured":"Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108(9):3701\u20136. https:\/\/doi.org\/10.1073\/pnas.1017385108.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"15","key":"2266_CR37","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1212\/WNL.0000000000000317","volume":"82","author":"M Araki","year":"2014","unstructured":"Araki M, Matsuoka T, Miyamoto K, Kusunoki S, Okamoto T, Murata M, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology. 2014;82(15):1302\u20136. https:\/\/doi.org\/10.1212\/WNL.0000000000000317.","journal-title":"Neurology."},{"issue":"1","key":"2266_CR38","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12974-018-1333-z","volume":"15","author":"T Duan","year":"2018","unstructured":"Duan T, Smith AJ, Verkman AS. Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflammation. 2018;15(1):294. https:\/\/doi.org\/10.1186\/s12974-018-1333-z.","journal-title":"J Neuroinflammation"},{"issue":"3","key":"2266_CR39","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nri1032","volume":"3","author":"JA Bluestone","year":"2003","unstructured":"Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol. 2003;3(3):253\u20137. https:\/\/doi.org\/10.1038\/nri1032.","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"2266_CR40","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1007\/s10072-018-3248-y","volume":"39","author":"EB Cho","year":"2018","unstructured":"Cho EB, Cho HJ, Seok JM, Min JH, Kang ES, Kim BJ. The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder. Neurol Sci. 2018;39(3):543\u20139. https:\/\/doi.org\/10.1007\/s10072-018-3248-y.","journal-title":"Neurol Sci"},{"issue":"7738","key":"2266_CR41","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/s41586-018-0824-5","volume":"565","author":"M Ito","year":"2019","unstructured":"Ito M, Komai K, Mise-Omata S, Iizuka-Koga M, Noguchi Y, Kondo T, et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature. 2019;565(7738):246\u201350. https:\/\/doi.org\/10.1038\/s41586-018-0824-5.","journal-title":"Nature."},{"issue":"4","key":"2266_CR42","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1084\/jem.20082824","volume":"206","author":"KE Webster","year":"2009","unstructured":"Webster KE, Walters S, Kohler RE, Mrkvan T, Boyman O, Surh CD, et al. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J Exp Med. 2009;206(4):751\u201360. https:\/\/doi.org\/10.1084\/jem.20082824.","journal-title":"J Exp Med"},{"key":"2266_CR43","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3389\/fneur.2017.00281","volume":"8","author":"W Gao","year":"2017","unstructured":"Gao W, Li F, Zhou Z, Xu X, Wu Y, Zhou S, et al. IL-2\/Anti-IL-2 complex attenuates inflammation and BBB disruption in mice subjected to traumatic brain injury. Front Neurol. 2017;8:281. https:\/\/doi.org\/10.3389\/fneur.2017.00281.","journal-title":"Front Neurol"},{"issue":"3","key":"2266_CR44","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1177\/0271678X16648712","volume":"37","author":"K Zhou","year":"2017","unstructured":"Zhou K, Zhong Q, Wang YC, Xiong XY, Meng ZY, Zhao T, et al. Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia\/macrophage polarization through the IL-10\/GSK3beta\/PTEN axis. J Cereb Blood Flow Metab. 2017;37(3):967\u201379. https:\/\/doi.org\/10.1177\/0271678X16648712.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"12","key":"2266_CR45","doi-asserted-by":"publisher","first-page":"5558","DOI":"10.1073\/pnas.1814394116","volume":"116","author":"H Meng","year":"2019","unstructured":"Meng H, Zhao H, Cao X, Hao J, Zhang H, Liu Y, et al. Double-negative T cells remarkably promote neuroinflammation after ischemic stroke. Proc Natl Acad Sci U S A. 2019;116(12):5558\u201363. https:\/\/doi.org\/10.1073\/pnas.1814394116.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"2266_CR46","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.intimp.2014.06.037","volume":"22","author":"Z Yang","year":"2014","unstructured":"Yang Z, Yu A, Liu Y, Shen H, Lin C, Lin L, et al. Regulatory T cells inhibit microglia activation and protect against inflammatory injury in intracerebral hemorrhage. Int Immunopharmacol. 2014;22(2):522\u20135. https:\/\/doi.org\/10.1016\/j.intimp.2014.06.037.","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"2266_CR47","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s12974-019-1550-0","volume":"16","author":"TJ Kramer","year":"2019","unstructured":"Kramer TJ, Hack N, Bruhl TJ, Menzel L, Hummel R, Griemert EV, et al. Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-gamma gene expression in acute experimental traumatic brain injury. J Neuroinflammation. 2019;16(1):163. https:\/\/doi.org\/10.1186\/s12974-019-1550-0.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"2266_CR48","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1161\/CIRCRESAHA.115.303895","volume":"115","author":"J Weirather","year":"2014","unstructured":"Weirather J, Hofmann UD, Beyersdorf N, Ramos GC, Vogel B, Frey A, et al. Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte\/macrophage differentiation. Circ Res. 2014;115(1):55\u201367. https:\/\/doi.org\/10.1161\/CIRCRESAHA.115.303895.","journal-title":"Circ Res"},{"issue":"2","key":"2266_CR49","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/ni.2499","volume":"14","author":"MG Strainic","year":"2013","unstructured":"Strainic MG, Shevach EM, An F, Lin F, Medof ME. Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta1 signaling and induction of Foxp3(+) regulatory T cells. Nat Immunol. 2013;14(2):162\u201371. https:\/\/doi.org\/10.1038\/ni.2499.","journal-title":"Nat Immunol"},{"issue":"3","key":"2266_CR50","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1161\/CIRCRESAHA.119.316461","volume":"127","author":"M Sharma","year":"2020","unstructured":"Sharma M, Schlegel MP, Afonso MS, Brown EJ, Rahman K, Weinstock A, et al. Regulatory T cells license macrophage pro-resolving functions during atherosclerosis regression. Circ Res. 2020;127(3):335\u201353. https:\/\/doi.org\/10.1161\/CIRCRESAHA.119.316461.","journal-title":"Circ Res"},{"key":"2266_CR51","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.msard.2018.12.002","volume":"27","author":"Y Wu","year":"2019","unstructured":"Wu Y, Zhong L, Geng J. Neuromyelitis optica spectrum disorder: pathogenesis, treatment, and experimental models. Mult Scler Relat Disord. 2019;27:412\u20138. https:\/\/doi.org\/10.1016\/j.msard.2018.12.002.","journal-title":"Mult Scler Relat Disord"},{"issue":"3","key":"2266_CR52","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1002\/eji.200939613","volume":"40","author":"YY Setiady","year":"2010","unstructured":"Setiady YY, Coccia JA, Park PU. In vivo depletion of CD4(+)FOXP3(+) Treg cells by the PC61 anti-CD25 monoclonal antibody is mediated by Fc gamma RIII+ phagocytes. Eur J Immunol. 2010;40(3):780\u20136. https:\/\/doi.org\/10.1002\/eji.200939613.","journal-title":"Eur J Immunol"},{"issue":"13","key":"2266_CR53","first-page":"3128","volume":"59","author":"S Onizuka","year":"1999","unstructured":"Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 1999;59(13):3128\u201333.","journal-title":"Cancer Res"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-021-02266-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-021-02266-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-021-02266-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:04:09Z","timestamp":1631707449000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-021-02266-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2266"],"URL":"https:\/\/doi.org\/10.1186\/s12974-021-02266-0","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,15]]},"assertion":[{"value":"5 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by Tongji Hospital Research Ethics Committee (IRB ID: TJ-IRB20190502). All animal procedures were approved by the Institute of Animal Care Committee of Tongji Medical College, Huazhong University of Science and Technology, China.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"201"}}