{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:07:15Z","timestamp":1787011635894,"version":"build-2736575974"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Primary Sj\u00f6gren disease (SjD) is a chronic inflammatory autoimmune disorder characterized by lymphocyte proliferation and progressive damage to exocrine glands. Its pathogenesis is complex, and clinical treatment remains challenging. Regulatory T cells (Tregs), a subset of inhibitory T lymphocytes, play a pivotal role in maintaining peripheral immune tolerance and immune homeostasis. They are also critically involved in the pathogenesis and progression of various autoimmune diseases, including SjD. Consequently, modulating the proliferation, activation, and functional balance of Tregs holds significant promise for ameliorating the immune-inflammatory microenvironment in SjD and slowing disease progression. Recent studies have shown that mesenchymal stem cells (MSCs), fenofibrate, and metformin can promote Treg proliferation and improve their function, thereby restoring the Th17\/Treg immune balance. These interventions synergistically reduce inflammatory responses, downregulate abnormal immune activation, and alleviate tissue pathological damage, ultimately leading to significantly increased saliva and tear secretion. This review summarizes the regulatory mechanisms of Tregs in SjD based on recent literature and explores the potential of Treg-targeted therapeutic strategies for SjD, aiming to provide a theoretical basis for the development of novel treatment approaches for this disease.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1802660","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:46:32Z","timestamp":1776231992000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulatory T cells in primary sj\u00f6gren disease: regulatory mechanisms and therapeutic prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Wang","family":"Chengzhi","sequence":"first","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical College of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yifan","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Songwei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical College of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du","family":"Mengmeng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical College of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Keying","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical College of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical College of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-024-01493-z","article-title":"update on sj\u00f6gren\u2019s syndrome: diagnostics, treatment, and challenges","volume":"83","author":"Zehrfeld","year":"2024","journal-title":"Z Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12967-024-05993-z","article-title":"Genetic insight into dissecting the immunophenotypes and inflammatory profiles in the pathogenesis of sjogren syndrome","volume":"23","author":"Xu","year":"2025","journal-title":"J Transl Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-020-08793-7","article-title":"Immunobiology of T cells in sj\u00f6gren\u2019s syndrome","volume":"60","author":"Yao","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2022.105406","article-title":"Current and future treatment in primary sj\u00f6gren\u2019s syndrome - a still challenging development","volume":"89","author":"Ritter","year":"2022","journal-title":"Joint Bone Spine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.molimm.2022.04.006","article-title":"Sirolimus therapy restores the PD-1+ICOS+tfh:CD45RA-Foxp3high activated tfr cell balance in primary sj\u00f6gren\u2019s syndrome","volume":"147","author":"Wang","year":"2022","journal-title":"Mol Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1136\/annrheumdis-2019-eular.2936","article-title":"Sirolimus selectively increases circulating treg cell numbers and restores the Th17\/treg balance in rheumatoid arthritis patients with low disease activity or in DAS28 remission who previously received conventional disease-modifying anti-rheumatic drugs","volume":"38","author":"Niu","year":"2020","journal-title":"Clin Exp Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/all.15449","article-title":"Regulatory T cells and immunoglobulin E: A new therapeutic link for autoimmunity","volume":"77","author":"Palomares","year":"2022","journal-title":"Allergy"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091999","article-title":"TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo","volume":"207","author":"Gottschalk","year":"2010","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/cells12101359","article-title":"The role of regulatory T cells in the onset and progression of primary sj\u00f6gren\u2019s syndrome","volume":"12","author":"Blinova","year":"2023","journal-title":"Cells"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.08.012","article-title":"Induced regulatory T cells: their development, stability, and applications","volume":"37","author":"Kanamori","year":"2016","journal-title":"Trends Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2869","article-title":"A regulatory role for TGF-\u03b2 signaling in the establishment and function of the thymic medulla","volume":"15","author":"Hauri-Hohl","year":"2014","journal-title":"Nat Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.immuni.2009.03.019","article-title":"Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor","volume":"30","author":"Miyara","year":"2009","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1040215","article-title":"Blockade of TNF-\u03b1 signaling benefits cancer therapy by suppressing effector regulatory T cell expansion","volume":"4","author":"Chang","year":"2015","journal-title":"Oncoimmunology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2174\/1573397113666170125122858","article-title":"Unique phenotypes and functions of follicular helper T cells and regulatory T cells in sj\u00f6gren\u2019s syndrome","volume":"14","author":"Saito","year":"2018","journal-title":"Curr Rheumatol Rev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103259","article-title":"Type I interferon signaling is required for dacryoadenitis in the nonobese diabetic mouse model of sj\u00f6gren syndrome","volume":"19","author":"Chaly","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.04.022","article-title":"Costimulatory and coinhibitory receptor pathways in infectious disease","volume":"44","author":"Attanasio","year":"2016","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1186\/s13287-021-02541-0","article-title":"Labial gland-derived mesenchymal stem cells and their exosomes ameliorate murine sj\u00f6gren\u2019s syndrome by modulating the balance of treg and Th17 cells","volume":"12","author":"Li","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8813558","article-title":"The function and role of the Th17\/treg cell balance in inflammatory bowel disease","volume":"2020","author":"Yan","year":"2020","journal-title":"J Immunol Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.cell.2025.11.035","article-title":"Next steps in regulatory T cells: biology and clinical application","volume":"189","author":"Zou","year":"2026","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.ccell.2023.12.010","article-title":"Distinct spatiotemporal dynamics of CD8+ T cell-derived cytokines in the tumor microenvironment","volume":"42","author":"Hoekstra","year":"2024","journal-title":"Cancer Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.840610","article-title":"T cell metabolism in infection","volume":"13","author":"Wik","year":"2022","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.immuni.2022.12.008","article-title":"Microenvironment-driven metabolic adaptations guiding CD8+ T cell anti-tumor immunity","volume":"56","author":"Park","year":"2023","journal-title":"Immunity"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00043","article-title":"Past, present, and future of regulatory T cell therapy in transplantation and autoimmunity","volume":"10","author":"Romano","year":"2019","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000778","article-title":"Double-negative T cells in autoimmune diseases","volume":"33","author":"Li","year":"2021","journal-title":"Curr Opin Rheumatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.02.001","article-title":"TCR\u03b1\u03b2+CD3+CD4-CD8- (double negative) T cells in autoimmunity","volume":"17","author":"Brandt","year":"2018","journal-title":"Autoimmun Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201511","article-title":"IL-17-producing CD4-CD8- T cells are expanded in the peripheral blood, infiltrate salivary glands and are resistant to corticosteroids in patients with primary sj\u00f6gren\u2019s syndrome","volume":"72","author":"Alunno","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3892\/mmr.2020.11681","article-title":"Mesenchymal stem cells negatively regulate CD4+ T cell activation in patients with primary sj&ouml;gren syndrome through the miRNA-125b and miRNA-155 TCR pathway","volume":"23","author":"Gong","year":"2021","journal-title":"Mol Med Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.52253","article-title":"Dermatological manifestations in patients with chronic kidney disease: a review","volume":"16","author":"Arriaga Escamilla","year":"2024","journal-title":"Cureus"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12649","article-title":"Expression of interleukin-17 in primary sj\u00f6gren\u2019s syndrome and the correlation with disease severity: a systematic review and meta-analysis","volume":"87","author":"Zhang","year":"2018","journal-title":"Scand J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.019","article-title":"The T cell in Sjogren\u2019s syndrome: force majeure, not spectateur","volume":"39","author":"Singh","year":"2012","journal-title":"J Autoimmun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1468469","article-title":"Subpopulation dynamics of T and B lymphocytes in sj\u00f6gren\u2019s syndrome: implications for disease activity and treatment","volume":"15","author":"Meng","year":"2024","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030730","article-title":"The balance of Th17 versus treg cells in autoimmunity","volume":"19","author":"Lee","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez004","article-title":"T cells in primary sj\u00f6gren\u2019s syndrome: targets for early intervention","volume":"60","author":"Verstappen","year":"2021","journal-title":"Rheumatol Oxf Engl"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000473","article-title":"Current views on the pathogenesis of sj\u00f6gren\u2019s syndrome","volume":"30","author":"Pontarini","year":"2018","journal-title":"Curr Opin Rheumatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1603305","article-title":"Reduced circulating regulatory T cells in primary sj\u00f6gren\u2019s syndrome: the contribution of enhanced apoptosis and impaired survival","volume":"16","author":"Wang","year":"2025","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1177\/0961203307085248","article-title":"Decreased CD4+CD25+bright T cells in peripheral blood of patients with primary Sjogren\u2019s syndrome","volume":"17","author":"Liu","year":"2008","journal-title":"Lupus"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.12.004","article-title":"Th17 and regulatory T cell balance in autoimmune and inflammatory diseases","volume":"13","author":"Noack","year":"2014","journal-title":"Autoimmun Rev"},{"key":"B38","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.molimm.2024.08.003","article-title":"Altered characteristics of regulatory T cells in target tissues of sj\u00f6gren\u2019s syndrome in murine models","volume":"174","author":"Zhou","year":"2024","journal-title":"Mol Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15565","article-title":"Altered subgroups of regulatory T cells in patients with primary sj\u00f6gren\u2019s syndrome","volume":"9","author":"Lin","year":"2023","journal-title":"Heliyon"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ado4856","article-title":"IFN-\u03b3-producing Th1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of sj\u00f6gren\u2019s disease","volume":"16","author":"Wang","year":"2024","journal-title":"Sci Transl Med"},{"key":"B41","unstructured":"GSE253188 - regulatory T cells and IFN-\u03b3-producing Th1 cells play a critical role in the pathogenesis of sj\u00f6gren\u2019s syndrome - OmicsDI"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.23.576314","article-title":"Regulatory T cells and IFN-\u03b3-producing Th1 cells play a critical role in the pathogenesis of sj\u00f6gren\u2019s syndrome","author":"Wang","year":"2024","journal-title":"BioRxiv Prepr Serv Biol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1053\/sarh.2002.33724","article-title":"Th1\/Th2 cytokine imbalance in patients with Sj\u00f6gren syndrome secondary to hepatitis C virus infection","volume":"32","author":"Ramos-Casals","year":"2002","journal-title":"Semin Arthritis Rheum"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/srep23561","article-title":"Altered mucosal microbiome diversity and disease severity in sj\u00f6gren syndrome","volume":"6","author":"de Paiva","year":"2016","journal-title":"Sci Rep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6070065","article-title":"T helper 17 cells in primary sj\u00f6gren\u2019s syndrome","volume":"6","author":"Matsui","year":"2017","journal-title":"J Clin Med"},{"key":"B46","unstructured":"Mitochondrial oxidative damage underlies regulatory T cell defects in autoimmunity"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-120550","article-title":"Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling","volume":"23","author":"Mukhopadhyay","year":"2009","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"13233","DOI":"10.1038\/s41598-018-31666-1","article-title":"Sphingosine kinases promote IL-17 expression in human T lymphocytes","volume":"8","author":"Barra","year":"2018","journal-title":"Sci Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/path.2694","article-title":"Autophagy: assays and artifacts","volume":"221","author":"Barth","year":"2010","journal-title":"J Pathol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.molimm.2019.02.004","article-title":"Autophagy in regulatory T cells: a double-edged sword in disease settings","volume":"109","author":"Zhang","year":"2019","journal-title":"Mol Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113514","article-title":"Sphingosine-1-phosphate alleviates Sj\u00f6gren\u2019s syndrome-like symptoms via inducing autophagy and regulating status of Treg cells in NOD mice","volume":"143","author":"Jin","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.immuni.2009.04.017","article-title":"Deltex1 is a target of the transcription factor NFAT that promotes T cell anergy","volume":"31","author":"Hsiao","year":"2009","journal-title":"Immunity"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/rtj93o","article-title":"Reduced Deltex1 expression in T cells indicates increased disease activity in sj\u00f6gren\u2019s disease","volume":"42","author":"Tsai","year":"2024","journal-title":"Clin Exp Rheumatol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"241ra78","DOI":"10.1126\/scitranslmed.3008895","article-title":"In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response","volume":"6","author":"Kasagi","year":"2014","journal-title":"Sci Transl Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/art.42244","article-title":"In vivo generation of SSA\/ro antigen-specific regulatory T cells improves experimental sj\u00f6gren\u2019s syndrome in mice","volume":"74","author":"Xu","year":"2022","journal-title":"Arthritis Rheumatol Hoboken NJ"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcu033","article-title":"Mesenchymal stem cells, autoimmunity and rheumatoid arthritis","volume":"107","author":"El-Jawhari","year":"2014","journal-title":"QJM Mon J Assoc Physicians"},{"key":"B57","unstructured":"Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical sj\u00f6gren syndrome"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4313","article-title":"Effect of mesenchymal stem cells on sj\u00f6gren-like mice and the microRNA expression profiles of splenic CD4+ T cells","volume":"13","author":"Ruan","year":"2017","journal-title":"Exp Ther Med"},{"key":"B59","doi-asserted-by":"publisher","first-page":"186\u2013196","DOI":"10.1080\/14397595.2019.1707996","article-title":"Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in Sj\u00f6gren\u2019s syndrome by inducing regulatory T cells","volume":"31","author":"Y","year":"2021","journal-title":"Mod Rheumatol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0844","article-title":"Immune regulatory properties of allogeneic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes","volume":"61","author":"Bassi","year":"2012","journal-title":"Diabetes"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1076","article-title":"Concise review: adipose-derived stem cells as a novel tool for future regenerative medicine","volume":"30","author":"Mizuno","year":"2012","journal-title":"Stem Cells Dayt Ohio"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003080","article-title":"The dual function cytokine IL-33 interacts with the transcription factor NF-\u03baB to dampen NF-\u03baB-stimulated gene transcription","volume":"187","author":"Ali","year":"2011","journal-title":"J Immunol Baltim Md 1950"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102446","article-title":"Adipose-mesenchymal stromal cells suppress experimental sj\u00f6gren syndrome by IL-33-driven expansion of ST2+ regulatory T cells","volume":"24","author":"Liu","year":"2021","journal-title":"iScience"},{"key":"B64","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/j.0105-2896.2004.00203.x","article-title":"Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways","volume":"202","author":"Kovanen","year":"2004","journal-title":"Immunol Rev"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090357","article-title":"The biology of interleukin-2","volume":"26","author":"Malek","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"B66","article-title":"Serum soluble interleukin-2 receptor is a useful biomarker for disease activity but not for differential diagnosis in IgG4-related disease and primary sj\u00f6gren\u2019s syndrome adults from a defined population","volume":"36","author":"Akiyama","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s13075-022-02769-y","article-title":"Impaired activation of STAT5 upon IL-2 stimulation in tregs and elevated sIL-2R in sj\u00f6gren\u2019s syndrome","volume":"24","author":"Keindl","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4357865","article-title":"Mesenchymal stem cells in primary sj\u00f6gren\u2019s syndrome: prospective and challenges","volume":"2018","author":"Chen","year":"2018","journal-title":"Stem Cells Int"},{"key":"B69","article-title":"Mesenchymal stromal cells attenuate multiple sclerosis via IDO-dependent increasing the suppressive proportion of CD5+ IL-10+ B cells","volume":"11","author":"Li","year":"2019","journal-title":"Am J Transl Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3134543","article-title":"Delivery of bone marrow-derived mesenchymal stem cells improves tear production in a mouse model of sj\u00f6gren\u2019s syndrome","volume":"2017","author":"Aluri","year":"2017","journal-title":"Stem Cells Int"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13113","article-title":"Stem cells from exfoliated deciduous teeth alleviate hyposalivation caused by sj\u00f6gren syndrome","volume":"25","author":"Du","year":"2019","journal-title":"Oral Dis"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.1139","article-title":"Human umbilical cord mesenchymal stem cells improve disease characterization of sjogren\u2019s syndrome in NOD mice through regulation of gut microbiota and treg\/Th17 cellular immunity","volume":"12","author":"Zou","year":"2024","journal-title":"Immun Inflammation Dis"},{"key":"B73","unstructured":"Characteristics of labial gland mesenchymal stem cells of healthy individuals and patients with sj\u00f6gren\u2019s syndrome: a preliminary study"},{"key":"B74","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s13287-021-02236-6","article-title":"Secreted factors from dental pulp stem cells improve sj\u00f6gren\u2019s syndrome via regulatory T cell-mediated immunosuppression","volume":"12","author":"Matsumura-Kawashima","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235900","article-title":"Diagnostic cytokines and comparative analysis secreted from exfoliated deciduous teeth, dental pulp, and bone marrow derived mesenchymal stem cells for functional cell-based therapy","volume":"20","author":"Yamada","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B76","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.reth.2021.01.006","article-title":"Dental pulp-derived stem cell-conditioned media attenuates secondary sj\u00f6gren\u2019s syndrome via suppression of inflammatory cytokines in the submandibular glands","volume":"16","author":"Ogata","year":"2021","journal-title":"Regener Ther"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01081","article-title":"The gut microbiota in immune-mediated inflammatory diseases","volume":"7","author":"Forbes","year":"2016","journal-title":"Front Microbiol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nature18848","article-title":"The microbiota in adaptive immune homeostasis and disease","volume":"535","author":"Honda","year":"2016","journal-title":"Nature"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2015.1072243","article-title":"Diminished salivary epidermal growth factor secretion: a link between sj\u00f6gren\u2019s syndrome and autoimmune gastritis","volume":"45","author":"Koskenpato","year":"2016","journal-title":"Scand J Rheumatol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228733","article-title":"Connection between the gut microbiome, systemic inflammation, gut permeability and FOXP3 expression in patients with primary sj\u00f6gren\u2019s syndrome","volume":"21","author":"Cano-Ortiz","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-024-09566-6","article-title":"USP18-mediated protein stabilization of NOTCH1 is associated with altered Th17\/Treg cell ratios and B cell-mediated autoantibody secretion in Sj\u00f6gren syndrome","volume":"73","author":"Jin","year":"2024","journal-title":"Immunol Res"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/330173a0","article-title":"A new immunomodulating compound (AS-101) with potential therapeutic application","volume":"330","author":"Sredni","year":"1987","journal-title":"Nature"},{"key":"B83","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.cviu.2013.12.011","article-title":"Fast and accurate near-duplicate image search with affinity propagation on the ImageWeb","volume":"124","author":"Xie","year":"2014","journal-title":"Comput Vis Image Underst"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.109937","article-title":"AS101 regulates the teff\/treg balance to alleviate rabbit autoimmune dacryoadenitis through modulating NFATc2","volume":"244","author":"Wang","year":"2024","journal-title":"Exp Eye Res"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2007.01825.x","article-title":"PPARs and their metabolic modulation: new mechanisms for transcriptional regulation","volume":"262","author":"Ahmed","year":"2007","journal-title":"J Intern Med"},{"key":"B86","doi-asserted-by":"publisher","first-page":"64","DOI":"10.5114\/ceji.2016.58817","article-title":"Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating treg\/Th17 disorder","volume":"41","author":"Cheng","year":"2016","journal-title":"Cent-Eur J Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102723","article-title":"Liver X receptor beta deficiency attenuates autoimmune-associated neuroinflammation in a T cell-dependent manner","volume":"124","author":"Bogie","year":"2021","journal-title":"J Autoimmun"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.6.12","article-title":"PPAR-\u03b1 agonist fenofibrate ameliorates sj\u00f6gren syndrome-like dacryoadenitis by modulating Th1\/Th17 and treg cell responses in NOD mice","volume":"63","author":"Guo","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B89","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.intimp.2013.03.020","article-title":"Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis","volume":"16","author":"Kang","year":"2013","journal-title":"Int Immunopharmacol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s13075-019-1904-0","article-title":"Metformin improves salivary gland inflammation and hypofunction in murine Sj\u00f6gren\u2019s syndrome","volume":"21","author":"Kim","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.02.068","article-title":"Dietary nitrate protects submandibular gland from hyposalivation in ovariectomized rats via suppressing cell apoptosis","volume":"497","author":"Xu","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116633109","article-title":"Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane","volume":"109","author":"Qin","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B93","doi-asserted-by":"publisher","first-page":"3323\u201335","DOI":"10.1111\/odi.70004","article-title":"Nitrate prevents sj\u00f6gren\u2019s disease by modulating T helper cells via NF-\u03baB pathway suppression","volume":"31","author":"Du","year":"2025","journal-title":"Oral Dis"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1110900","article-title":"The yin and yang of interleukin-2-mediated immunotherapy","volume":"365","author":"Bluestone","year":"2011","journal-title":"N Engl J Med"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.03.016","article-title":"Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction","volume":"28","author":"Tang","year":"2008","journal-title":"Immunity"},{"key":"B96","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S2213-8587(13)70113-X","article-title":"Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1\/2 randomised, double-blind, placebo-controlled trial","volume":"1","author":"Hartemann","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105143","article-title":"Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis","volume":"365","author":"Saadoun","year":"2011","journal-title":"N Engl J Med"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.887354","article-title":"Low dose interleukin-2 ameliorates sj\u00f6gren\u2019s syndrome in a murine model","volume":"9","author":"Wang","year":"2022","journal-title":"Front Med"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2117112119","article-title":"HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation","volume":"119","author":"Cheung","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-019-00694-1","article-title":"Upregulation of RUNX1 suppresses proliferation and migration through repressing VEGFA expression in hepatocellular carcinoma","volume":"26","author":"Liu","year":"2020","journal-title":"Pathol Oncol Res POR"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2025.152910","article-title":"Exploring the role of diosgenin in modulating RUNX1 and HIPK2 transcription to mitigate primary sj\u00f6gren\u2019s syndrome","volume":"230","author":"Pan","year":"2025","journal-title":"Immunobiology"},{"key":"B102","doi-asserted-by":"publisher","first-page":"6156","DOI":"10.1038\/s41598-020-62881-4","article-title":"Oral therapy with colonization factor antigen I prevents development of type 1 diabetes in non-obese diabetic mice","volume":"10","author":"Nelson","year":"2020","journal-title":"Sci Rep"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100530","article-title":"Segregated regulatory CD39+CD4+ T cell function: TGF-\u03b2-producing Foxp3- and IL-10-producing Foxp3+ cells are interdependent for protection against collagen-induced arthritis","volume":"187","author":"Kochetkova","year":"2011","journal-title":"J Immunol Baltim Md 1950"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302018","article-title":"Oral escherichia coli colonization factor antigen I fimbriae ameliorate arthritis via IL-35, not IL-27","volume":"192","author":"Kochetkova","year":"2014","journal-title":"J Immunol Baltim Md 1950"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02691","article-title":"Delivery of IL-35 by lactococcus lactis ameliorates collagen-induced arthritis in mice","volume":"9","author":"Maddaloni","year":"2018","journal-title":"Front Immunol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13075-021-02475-1","article-title":"Stimulation of regulatory T cells with Lactococcus lactis expressing enterotoxigenic E. coli colonization factor antigen 1 retains salivary flow in a genetic model of Sj\u00f6gren\u2019s syndrome","volume":"23","author":"Akgul","year":"2021","journal-title":"Arthritis Res Ther"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1802660\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:46:34Z","timestamp":1776231994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1802660\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":106,"alternative-id":["10.3389\/fimmu.2026.1802660"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1802660","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1802660"}}