{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:14:05Z","timestamp":1793121245236,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The study aimed to explore the mechanism of artemisinin in treating primary Sj\u00f6gren\u2019s syndrome (pSS) based on network pharmacology and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD\/Ltj mice to validate the efficacy and critical mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD\/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD\/Ltj model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12865-024-00605-3","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T01:02:37Z","timestamp":1707699757000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1186","volume":"25","author":[{"given":"Jia-he","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-wei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-bo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-ying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-jiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-wen","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"605_CR1","doi-asserted-by":"crossref","unstructured":"Negrini S, Emmi G, Greco M, Borro M, Sardanelli F, Murdaca G, et al. Sj\u00f6gren's syndrome: a systemic autoimmune disease. Clin Exp Med. 2022;22(1).","DOI":"10.1007\/s10238-021-00728-6"},{"issue":"Suppl 118","key":"605_CR2","first-page":"123","volume":"37","author":"A Goules","year":"2019","unstructured":"Goules A, Geetha D, Arend LJ, Baer AN. Renal involvement in primary Sj\u00f6gren\u2019s syndrome: natural history and treatment outcome. Clin Exp Rheumatol. 2019;37(Suppl 118):123\u201332.","journal-title":"Clin Exp Rheumatol"},{"key":"605_CR3","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3389\/fmed.2020.00138","volume":"7","author":"F Dai","year":"2020","unstructured":"Dai F, Yang G, Rao P, Wu P, Chen R, Sun Y, et al. Clinical characteristics of secondary immune thrombocytopenia associated with primary Sj\u00f6gren\u2019s syndrome. Front Med (Lausanne). 2020;7:138.","journal-title":"Front Med (Lausanne)"},{"issue":"Suppl 126","key":"605_CR4","first-page":"291","volume":"38","author":"F Luppi","year":"2020","unstructured":"Luppi F, Sebastiani M, Silva M, Sverzellati N, Cavazza A, Salvarani C, et al. Interstitial lung disease in Sj\u00f6gren\u2019s syndrome: a clinical review. Clin Exp Rheumatol. 2020;38(Suppl 126):291\u2013300.","journal-title":"Clin Exp Rheumatol"},{"key":"605_CR5","first-page":"247","volume":"6","author":"R Patel","year":"2014","unstructured":"Patel R, Shahane A. The epidemiology of Sj\u00f6gren\u2019s syndrome. Clin Epidemiol. 2014;6:247\u201355.","journal-title":"Clin Epidemiol"},{"key":"605_CR6","doi-asserted-by":"publisher","first-page":"5928232","DOI":"10.1155\/2021\/5928232","volume":"2021","author":"Y Tian","year":"2021","unstructured":"Tian Y, Yang H, Liu N, Li Y, Chen J. Advances in pathogenesis of Sj\u00f6gren\u2019s syndrome. J Immunol Res. 2021;2021:5928232.","journal-title":"J Immunol Res"},{"issue":"Suppl 126","key":"605_CR7","first-page":"315","volume":"38","author":"S Fasano","year":"2020","unstructured":"Fasano S, Mauro D, Macaluso F, Xiao F, Zhao Y, Lu L, et al. Pathogenesis of primary Sj\u00f6gren\u2019s syndrome beyond B lymphocytes. Clin Exp Rheumatol. 2020;38(Suppl 126):315\u201323.","journal-title":"Clin Exp Rheumatol"},{"key":"605_CR8","doi-asserted-by":"crossref","unstructured":"Ramos-Casals M, Brito-Zer\u00f3n P, Bombardieri S, Bootsma H, De Vita S, D\u00f6rner T, et al. EULAR recommendations for the management of Sj\u00f6gren's syndrome with topical and systemic therapies. Ann Rheum Dis. 2020;79(1).","DOI":"10.1136\/annrheumdis-2019-216114"},{"key":"605_CR9","doi-asserted-by":"crossref","unstructured":"van Beers JJBC, Damoiseaux JGMC. Immune monitoring upon treatment with biologics in Sj\u00f6gren's syndrome: the what, where, when, and how. Biomolecules. 2021;11(1).","DOI":"10.3390\/biom11010116"},{"key":"605_CR10","doi-asserted-by":"publisher","first-page":"205031212312216","DOI":"10.1177\/20503121231221633","volume":"12","author":"L Zhao","year":"2024","unstructured":"Zhao L, Wang Z, Xu M, Xing Y, Kong X. Characteristics of primary Sjogren\u2019s syndrome with articular manifestations at initial treatment. SAGE Open Med. 2024;12:20503121231221630.","journal-title":"SAGE Open Med"},{"issue":"8","key":"605_CR11","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/s41584-021-00634-x","volume":"17","author":"R Seror","year":"2021","unstructured":"Seror R, Nocturne G, Mariette X. Current and future therapies for primary Sj\u00f6gren syndrome. Nat Rev Rheumatol. 2021;17(8):475\u201386.","journal-title":"Nat Rev Rheumatol"},{"key":"605_CR12","doi-asserted-by":"crossref","unstructured":"Cafaro G, Bursi R, Chatzis LG, Fulvio G, Ferro F, Bartoloni E, et al. One year in review 2021: Sj\u00f6gren's syndrome. Clin Exp Rheumatol. 2021;39(Suppl 133).","DOI":"10.55563\/clinexprheumatol\/eojaol"},{"issue":"12","key":"605_CR13","first-page":"2343","volume":"41","author":"S Longhino","year":"2023","unstructured":"Longhino S, Chatzis LG, Dal Pozzolo R, Peretti S, Fulvio G, La Rocca G, et al. Sj\u00f6gren\u2019s syndrome: one year in review 2023. Clin Exp Rheumatol. 2023;41(12):2343\u201356.","journal-title":"Clin Exp Rheumatol"},{"issue":"1","key":"605_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11684-021-0898-6","volume":"16","author":"Q Shi","year":"2022","unstructured":"Shi Q, Xia F, Wang Q, Liao F, Guo Q, Xu C, et al. Discovery and repurposing of artemisinin. Front Med. 2022;16(1):1\u20139.","journal-title":"Front Med"},{"key":"605_CR15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.semcancer.2017.02.009","volume":"46","author":"T Efferth","year":"2017","unstructured":"Efferth T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017;46:65\u201383.","journal-title":"Semin Cancer Biol"},{"issue":"1","key":"605_CR16","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.pharmthera.2013.12.001","volume":"142","author":"WE Ho","year":"2014","unstructured":"Ho WE, Peh HY, Chan TK, Wong WSF. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014;142(1):126\u201339.","journal-title":"Pharmacol Ther"},{"issue":"8","key":"605_CR17","doi-asserted-by":"publisher","first-page":"e104762","DOI":"10.1371\/journal.pone.0104762","volume":"9","author":"L Hou","year":"2014","unstructured":"Hou L, Block KE, Huang H. Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis. PLoS One. 2014;9(8):e104762.","journal-title":"PLoS One"},{"issue":"5","key":"605_CR18","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/sj.bjp.0707137","volume":"150","author":"J-X Wang","year":"2007","unstructured":"Wang J-X, Tang W, Shi L-P, Wan J, Zhou R, Ni J, et al. Investigation of the immunosuppressive activity of artemether on T-cell activation and proliferation. Br J Pharmacol. 2007;150(5):652\u201361.","journal-title":"Br J Pharmacol"},{"issue":"8","key":"605_CR19","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1002\/art.30392","volume":"63","author":"L-F Hou","year":"2011","unstructured":"Hou L-F, He S-J, Li X, Yang Y, He P-L, Zhou Y, et al. Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL\/lpr mice by inhibiting Th1 and Th17 cell responses. Arthritis Rheum. 2011;63(8):2445\u201355.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"605_CR20","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.ajem.2015.12.075","volume":"34","author":"H Long","year":"2016","unstructured":"Long H, Xu B, Luo Y, Luo K. Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation. Am J Emerg Med. 2016;34(5):772\u20137.","journal-title":"Am J Emerg Med"},{"key":"605_CR21","first-page":"1826299","volume":"2022","author":"G-Y Chen","year":"2022","unstructured":"Chen G-Y, Wang Y-F, Yu X-B, Liu X-Y, Chen J-Q, Luo J, et al. Network pharmacology-based strategy to investigate the mechanisms of Cibotium barometz in treating osteoarthritis. Evid Based Complement Alternat Med. 2022;2022:1826299.","journal-title":"Evid Based Complement Alternat Med"},{"key":"605_CR22","first-page":"7858925","volume":"2022","author":"G-Y Chen","year":"2022","unstructured":"Chen G-Y, Liu X-Y, Luo J, Yu X-B, Liu Y, Tao Q-W. Integrating network pharmacology and experimental validation to explore the key mechanism of Gubitong recipe in the treatment of osteoarthritis. Comput Math Methods Med. 2022;2022:7858925.","journal-title":"Comput Math Methods Med"},{"key":"605_CR23","doi-asserted-by":"publisher","first-page":"153381","DOI":"10.1016\/j.phymed.2020.153381","volume":"80","author":"T Zhan","year":"2021","unstructured":"Zhan T, Wang B, Fu J, Shao Y, Ye L, Shi H, et al. Artesunate inhibits Sj\u00f6gren\u2019s syndrome-like autoimmune responses and BAFF-induced B cell hyperactivation via TRAF6-mediated NF-\u03baB signaling. Phytomedicine. 2021;80:153381.","journal-title":"Phytomedicine."},{"issue":"4","key":"605_CR24","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10875-006-9022-6","volume":"26","author":"M Ram","year":"2006","unstructured":"Ram M, Sherer Y, Shoenfeld Y. Matrix metalloproteinase-9 and autoimmune diseases. J Clin Immunol. 2006;26(4):299\u2013307.","journal-title":"J Clin Immunol"},{"key":"605_CR25","doi-asserted-by":"crossref","unstructured":"Asatsuma M, Ito S, Watanabe M, Takeishi H, Nomura S, Wada Y, et al. Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 in saliva from patients with primary Sj\u00f6gren's syndrome. Clin Chim Acta. 2004;345(1-2).","DOI":"10.1016\/j.cccn.2004.03.006"},{"issue":"6","key":"605_CR26","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1007\/s10753-019-01079-x","volume":"42","author":"K Aota","year":"2019","unstructured":"Aota K, Ono S, Yamanoi T, Kani K, Momota Y, Azuma M. MMP-9 inhibition suppresses interferon-\u03b3-induced CXCL10 production in human salivary gland ductal cells. Inflammation. 2019;42(6):2148\u201358.","journal-title":"Inflammation."},{"key":"605_CR27","doi-asserted-by":"crossref","unstructured":"Patra R, Das NC, Mukherjee S. Exploring the differential expression and prognostic significance of the COL11A1 gene in human colorectal carcinoma: An integrated bioinformatics approach. Front Genet. 2021;12.","DOI":"10.3389\/fgene.2021.608313"},{"issue":"2","key":"605_CR28","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.bjid.2015.10.011","volume":"20","author":"S Mukherjee","year":"2016","unstructured":"Mukherjee S, Karmakar S, Babu SPS. TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis. 2016;20(2):193\u2013204.","journal-title":"Braz J Infect Dis"},{"issue":"8","key":"605_CR29","doi-asserted-by":"publisher","first-page":"e12476","DOI":"10.15252\/emmm.202012476","volume":"12","author":"EL Nirk","year":"2020","unstructured":"Nirk EL, Reggiori F, Mauthe M. Hydroxychloroquine in rheumatic autoimmune disorders and beyond. EMBO Mol Med. 2020;12(8):e12476.","journal-title":"EMBO Mol Med"},{"issue":"6","key":"605_CR30","doi-asserted-by":"publisher","first-page":"766","DOI":"10.6061\/clinics\/2013(06)07","volume":"68","author":"JC Silva","year":"2013","unstructured":"Silva JC, Mariz HA, Rocha LF, Oliveira PSS, Dantas AT, Duarte ALBP, et al. Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (Sao Paulo). 2013;68(6):766\u201371.","journal-title":"Clinics (Sao Paulo)"},{"issue":"1","key":"605_CR31","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s13075-017-1393-y","volume":"19","author":"S-F Wu","year":"2017","unstructured":"Wu S-F, Chang C-B, Hsu J-M, Lu M-C, Lai N-S, Li C, et al. Hydroxychloroquine inhibits CD154 expression in CD4+ T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017;19(1):183.","journal-title":"Arthritis Res Ther."},{"key":"605_CR32","doi-asserted-by":"publisher","first-page":"6357046","DOI":"10.1155\/2020\/6357046","volume":"2020","author":"A Dewitte","year":"2020","unstructured":"Dewitte A, Villeneuve J, Lepreux S, Bouchecareilh M, Gauthereau X, Rigothier C, et al. CD154 induces Interleukin-6 secretion by kidney tubular epithelial cells under hypoxic conditions: inhibition by chloroquine. Mediat Inflamm. 2020;2020:6357046.","journal-title":"Mediat Inflamm"},{"issue":"5","key":"605_CR33","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1136\/annrheumdis-2016-210012","volume":"76","author":"N M\u00fcller-Calleja","year":"2017","unstructured":"M\u00fcller-Calleja N, Manukyan D, Canisius A, Strand D, Lackner KJ. Hydroxychloroquine inhibits proinflammatory signalling pathways by targeting endosomal NADPH oxidase. Ann Rheum Dis. 2017;76(5):891\u20137.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"605_CR34","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1159\/000484955","volume":"44","author":"N An","year":"2017","unstructured":"An N, Chen Y, Wang C, Yang C, Wu Z-H, Xue J, et al. Chloroquine Autophagic inhibition rebalances Th17\/Treg-mediated immunity and ameliorates systemic lupus erythematosus. Cell Physiol Biochem. 2017;44(1):412\u201322.","journal-title":"Cell Physiol Biochem"},{"key":"605_CR35","doi-asserted-by":"publisher","first-page":"391","DOI":"10.3389\/fimmu.2019.00391","volume":"10","author":"L \u00c1lvarez-Rodr\u00edguez","year":"2019","unstructured":"\u00c1lvarez-Rodr\u00edguez L, Mart\u00ednez-Taboada V, Calvo-Al\u00e9n J, Beares I, Villa I, L\u00f3pez-Hoyos M. Altered Th17\/Treg ratio in peripheral blood of systemic lupus erythematosus but not primary antiphospholipid syndrome. Front Immunol. 2019;10:391.","journal-title":"Front Immunol"},{"issue":"6","key":"605_CR36","doi-asserted-by":"publisher","first-page":"818","DOI":"10.3899\/jrheum.170737","volume":"45","author":"J Yang","year":"2018","unstructured":"Yang J, Yang X, Yang J, Li M. Hydroxychloroquine inhibits the differentiation of Th17 cells in systemic lupus erythematosus. J Rheumatol. 2018;45(6):818\u201326.","journal-title":"J Rheumatol"},{"issue":"8","key":"605_CR37","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s40261-018-0656-y","volume":"38","author":"D Plantone","year":"2018","unstructured":"Plantone D, Koudriavtseva T. Current and future use of chloroquine and Hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a Mini-review. Clin Drug Investig. 2018;38(8):653\u201371.","journal-title":"Clin Drug Investig"},{"issue":"9","key":"605_CR38","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nrrheum.2013.110","volume":"9","author":"G Nocturne","year":"2013","unstructured":"Nocturne G, Mariette X. Advances in understanding the pathogenesis of primary Sj\u00f6gren\u2019s syndrome. Nat Rev Rheumatol. 2013;9(9):544\u201356.","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"605_CR39","first-page":"263","volume":"27","author":"G Sudzius","year":"2013","unstructured":"Sudzius G, Mieliauskaite D, Butrimiene I, Siaurys A, Mackiewicz Z, Dumalakiene I. Activity of T-helper cells in patients with primary Sjogren\u2019s syndrome. In Vivo. 2013;27(2):263\u20138.","journal-title":"In Vivo"},{"issue":"9","key":"605_CR40","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1002\/eji.202048794","volume":"51","author":"W Zhang","year":"2021","unstructured":"Zhang W, Liu X, Zhu Y, Liu X, Gu Y, Dai X, et al. Transcriptional and posttranslational regulation of Th17\/Treg balance in health and disease. Eur J Immunol. 2021;51(9):2137\u201350.","journal-title":"Eur J Immunol"},{"issue":"6","key":"605_CR41","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.autrev.2013.12.004","volume":"13","author":"M Noack","year":"2014","unstructured":"Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13(6):668\u201377.","journal-title":"Autoimmun Rev"},{"issue":"2","key":"605_CR42","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00011-011-0419-1","volume":"61","author":"KE Graeber","year":"2012","unstructured":"Graeber KE, Olsen NJ. Th17 cell cytokine secretion profile in host defense and autoimmunity. Inflamm Res. 2012;61(2):87\u201396.","journal-title":"Inflamm Res"},{"issue":"6","key":"605_CR43","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","volume":"126","author":"II Ivanov","year":"2006","unstructured":"Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126(6):1121\u201333.","journal-title":"Cell."},{"key":"605_CR44","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaut.2017.11.003","volume":"87","author":"GM Verstappen","year":"2018","unstructured":"Verstappen GM, Corneth OBJ, Bootsma H, Kroese FGM. Th17 cells in primary Sj\u00f6gren\u2019s syndrome: pathogenicity and plasticity. J Autoimmun. 2018;87:16\u201325.","journal-title":"J Autoimmun"},{"issue":"2","key":"605_CR45","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/ni1552","volume":"9","author":"H-C Hsu","year":"2008","unstructured":"Hsu H-C, Yang P, Wang J, Wu Q, Myers R, Chen J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol. 2008;9(2):166\u201375.","journal-title":"Nat Immunol"},{"issue":"3","key":"605_CR46","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2174\/1573397113666170125122858","volume":"14","author":"M Saito","year":"2018","unstructured":"Saito M, Otsuka K, Ushio A, Yamada A, Arakaki R, Kudo Y, et al. Unique phenotypes and functions of follicular helper T cells and regulatory T cells in Sj\u00f6gren\u2019s syndrome. Curr Rheumatol Rev. 2018;14(3):239\u201345.","journal-title":"Curr Rheumatol Rev"},{"issue":"2","key":"605_CR47","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3109\/08830185.2013.863303","volume":"33","author":"L Passerini","year":"2014","unstructured":"Passerini L, Santoni de Sio FR, Roncarolo MG, Bacchetta R. Forkhead box P3: the peacekeeper of the immune system. Int Rev Immunol. 2014;33(2):129\u201345.","journal-title":"Int Rev Immunol"},{"issue":"1","key":"605_CR48","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1186\/s13287-021-02541-0","volume":"12","author":"B Li","year":"2021","unstructured":"Li B, Xing Y, Gan Y, He J, Hua H. Labial gland-derived mesenchymal stem cells and their exosomes ameliorate murine Sj\u00f6gren\u2019s syndrome by modulating the balance of Treg and Th17 cells. Stem Cell Res Ther. 2021;12(1):478.","journal-title":"Stem Cell Res Ther"},{"issue":"5","key":"605_CR49","doi-asserted-by":"publisher","first-page":"e12873","DOI":"10.1111\/sji.12873","volume":"91","author":"Z Wan","year":"2020","unstructured":"Wan Z, Zhou Z, Liu Y, Lai Y, Luo Y, Peng X, et al. Regulatory T cells and T helper 17 cells in viral infection. Scand J Immunol. 2020;91(5):e12873.","journal-title":"Scand J Immunol"},{"issue":"4","key":"605_CR50","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2011.03.018","volume":"34","author":"A Chaudhry","year":"2011","unstructured":"Chaudhry A, Samstein Robert M, Treuting P, Liang Y, Pils Marina C, Heinrich J-M, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34(4):566\u201378.","journal-title":"Immunity."},{"issue":"7090","key":"605_CR51","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(7090):235\u20138.","journal-title":"Nature."},{"issue":"7192","key":"605_CR52","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/nature06878","volume":"453","author":"L Zhou","year":"2008","unstructured":"Zhou L, Lopes JE, Chong MMW, Ivanov II, Min R, Victora GD, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature. 2008;453(7192):236\u201340.","journal-title":"Nature."},{"issue":"4","key":"605_CR53","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.4049\/jimmunol.1201218","volume":"190","author":"G Cheng","year":"2013","unstructured":"Cheng G, Yu A, Dee MJ, Malek TR. IL-2R signaling is essential for functional maturation of regulatory T cells during thymic development. J Immunol. 2013;190(4):1567\u201375.","journal-title":"J Immunol"},{"issue":"3","key":"605_CR54","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.immuni.2007.02.009","volume":"26","author":"A Laurence","year":"2007","unstructured":"Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 2007;26(3):371\u201381.","journal-title":"Immunity."},{"issue":"24","key":"605_CR55","doi-asserted-by":"publisher","first-page":"6102","DOI":"10.1182\/blood-2008-12-195354","volume":"113","author":"MD Sharma","year":"2009","unstructured":"Sharma MD, Hou D-Y, Liu Y, Koni PA, Metz R, Chandler P, et al. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009;113(24):6102\u201311.","journal-title":"Blood."},{"key":"605_CR56","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.2147\/DDDT.S354946","volume":"16","author":"G-Y Chen","year":"2022","unstructured":"Chen G-Y, Luo J, Liu Y, Yu X-B, Liu X-Y, Tao Q-W. Network pharmacology analysis and experimental validation to investigate the mechanism of Total flavonoids of Rhizoma Drynariae in treating rheumatoid arthritis. Drug Des Devel Ther. 2022;16:1743\u201366.","journal-title":"Drug Des Devel Ther"},{"issue":"4","key":"605_CR57","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1111\/jcmm.12793","volume":"20","author":"A Alunno","year":"2016","unstructured":"Alunno A, Ibba-Manneschi L, Bistoni O, Rosa I, Caterbi S, Gerli R, et al. Mobilization of lymphatic endothelial precursor cells and lymphatic neovascularization in primary Sj\u00f6gren\u2019s syndrome. J Cell Mol Med. 2016;20(4):613\u201322.","journal-title":"J Cell Mol Med"},{"issue":"1","key":"605_CR58","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s13075-015-0714-2","volume":"17","author":"C Wu","year":"2015","unstructured":"Wu C, Wang Z, Zourelias L, Thakker H, Passineau MJ. IL-17 sequestration via salivary gland gene therapy in a mouse model of Sjogren\u2019s syndrome suppresses disease-associated expression of the putative autoantigen Klk1b22. Arthritis Res Ther. 2015;17(1):198.","journal-title":"Arthritis Res Ther."},{"issue":"2","key":"605_CR59","doi-asserted-by":"publisher","first-page":"R64","DOI":"10.1186\/ar3780","volume":"14","author":"S-K Kwok","year":"2012","unstructured":"Kwok S-K, Cho M-L, Her Y-M, Oh H-J, Park M-K, Lee S-Y, et al. TLR2 ligation induces the production of IL-23\/IL-17 via IL-6, STAT3 and NF-kB pathway in patients with primary Sjogren\u2019s syndrome. Arthritis Res Ther. 2012;14(2):R64.","journal-title":"Arthritis Res Ther"},{"issue":"7","key":"605_CR60","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1177\/0022034516634647","volume":"95","author":"LW Zhang","year":"2016","unstructured":"Zhang LW, Cong X, Zhang Y, Wei T, Su YC, Serr\u00e3o ACA, et al. Interleukin-17 impairs salivary tight junction integrity in Sj\u00f6gren\u2019s syndrome. J Dent Res. 2016;95(7):784\u201392.","journal-title":"J Dent Res"},{"key":"605_CR61","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1111\/j.1749-6632.2010.05825.x","volume":"1217","author":"Y Hu","year":"2011","unstructured":"Hu Y, Shen F, Crellin NK, Ouyang W. The IL-17 pathway as a major therapeutic target in autoimmune diseases. Ann N Y Acad Sci. 2011;1217:60\u201376.","journal-title":"Ann N Y Acad Sci"}],"container-title":["BMC Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12865-024-00605-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12865-024-00605-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12865-024-00605-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T02:02:52Z","timestamp":1707703372000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcimmunol.biomedcentral.com\/articles\/10.1186\/s12865-024-00605-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,12]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["605"],"URL":"https:\/\/doi.org\/10.1186\/s12865-024-00605-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2798691\/v1","asserted-by":"object"}]},"ISSN":["1471-2172"],"issn-type":[{"value":"1471-2172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,12]]},"assertion":[{"value":"10 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiment procedures were approved by the Animal Care and Welfare Committee of Beijing University of Chinese Medicine (No. BUCM-4-2021090307-3158). All methods were carried out in accordance with relevant guidelines and regulations.","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 no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16"}}