{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:04:08Z","timestamp":1790960648106,"version":"4.1.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701600"],"award-info":[{"award-number":["81701600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ17H100001"],"award-info":[{"award-number":["LQ17H100001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LGF18H100001"],"award-info":[{"award-number":["LGF18H100001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Medical and Health Program of Zhejiang Province","award":["2019RC032"],"award-info":[{"award-number":["2019RC032"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701600"],"award-info":[{"award-number":["81701600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ17H100001"],"award-info":[{"award-number":["LQ17H100001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LGF18H100001"],"award-info":[{"award-number":["LGF18H100001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) is a chronic autoimmune disease, characterized by lymphocytic infiltration into exocrine glands, which causes dry eyes, dry mouth, and systemic damage. Although the precise etiology of pSS is not clear yet, highly activated B cells, abundant anti-SSA\/Ro, and anti-SSB\/La autoantibodies are the hallmarks of this disease. Follicular helper T cells (Tfh), a subset of CD4+T cells, with cell surface receptors PD-1 and CXCR5, express ICOS, transcription factor Bcl-6, and a cytokine IL-21. These cells help in the differentiation of B cells into plasma cells and stimulate the formation of germinal center (GC). Previous studies have demonstrated abundant Tfh cells in the peripheral blood and salivary glands (SGs) of the patients with pSS, correlated with extensive lymphocytic infiltration of the SGs and high disease activity scores. Patients with pSS who are treated with abatacept (CTLA-4 Ig) show fewer circulating Tfh cells, reduced expression of ICOS, and lower disease activity scores. Recently identified follicular regulatory T (Tfr) cells, a subset of regulatory T cells, control the function of Tfh cells and the GC reactions. Here, we summarize the observed alterations in Tfh and Tfr cell numbers, activation state, and circulating subset distribution in pSS. Our goal is to improve the understanding of the roles of Tfh and Tfr cells (surface marker expression, cytokine production, and transcription factors) in the pathogenesis of pSS, thus contributing to the identification of candidate therapeutic agents for this disease.<\/jats:p>","DOI":"10.1002\/jlb.5mr1020-057rr","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T07:42:30Z","timestamp":1608104550000},"page":"437-447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Follicular helper T cells and follicular regulatory T cells in the immunopathology of primary Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1093","volume":"109","author":[{"given":"Weiqian","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Rheumatology, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Diseases Diagnosis and Treatment, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilin","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Zhejiang Traditional Chinese Medicine and Western Medicine Hospital , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"2023032108374246700_jlb10861-cit-0001","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0140-6736(05)66990-5","article-title":"Sj\u00f6gren\u2019s syndrome","volume":"366","author":"Fox","year":"2005","journal-title":"Lancet"},{"key":"2023032108374246700_jlb10861-cit-0002","doi-asserted-by":"crossref","first-page":"16047","DOI":"10.1038\/nrdp.2016.47","article-title":"Sjogren syndrome","volume":"2","author":"Brito-Zeron","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"2023032108374246700_jlb10861-cit-0003","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1136\/annrheumdis-2014-205375","article-title":"Epidemiology of primary Sj\u00f6gren\u2019s syndrome: a systematic review and meta-analysis","volume":"74","author":"Qin","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"2023032108374246700_jlb10861-cit-0004","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1182\/blood-2007-10-119974","article-title":"Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium","volume":"111","author":"Ekstrom Smedby","year":"2008","journal-title":"Blood"},{"key":"2023032108374246700_jlb10861-cit-0005","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrrheum.2018.1","article-title":"B cells in the pathogenesis of primary Sj\u00f6gren syndrome","volume":"14","author":"Nocturne","year":"2018","journal-title":"Nat Rev Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0006","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.2174\/138920112802273100","article-title":"B-lymphocytes govern the pathogenesis of Sj\u00f6gren\u2019s syndrome","volume":"13","author":"Youinou","year":"2012","journal-title":"Curr Pharm Biotechnol"},{"key":"2023032108374246700_jlb10861-cit-0007","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nrrheum.2013.110","article-title":"Advances in understanding the pathogenesis of primary Sj\u00f6gren\u2019s syndrome","volume":"9","author":"Nocturne","year":"2013","journal-title":"Nat Rev Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0008","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrrheum.2014.225","article-title":"A pathogenetic role for IL-21 in primary Sj\u00f6gren syndrome","volume":"11","author":"Kwok","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0009","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nrrheum.2016.100","article-title":"Treatment of primary Sjogren syndrome","volume":"12","author":"Saraux","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0010","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMcp1702514","article-title":"Primary Sj\u00f6gren\u2019s Syndrome","volume":"378","author":"Mariette","year":"2018","journal-title":"N Engl J Med."},{"key":"2023032108374246700_jlb10861-cit-0011","doi-asserted-by":"crossref","first-page":"229","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":"2023032108374246700_jlb10861-cit-0012","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jaut.2012.01.002","article-title":"Pathogenesis of Sj\u00f6gren\u2019s syndrome: what we know and what we should learn","volume":"39","author":"Tzioufas","year":"2012","journal-title":"J Autoimmun"},{"key":"2023032108374246700_jlb10861-cit-0013","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jaut.2013.07.007","article-title":"T helper subsets in Sj\u00f6gren\u2019s syndrome and IgG4-related dacryoadenitis and sialoadenitis: a critical review","volume":"51","author":"Moriyama","year":"2014","journal-title":"J Autoimmun"},{"key":"2023032108374246700_jlb10861-cit-0014","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/ar2210","article-title":"B cells in Sj\u00f6gren\u2019s syndrome: indications for disturbed selection and differentiation in ectopic lymphoid tissue","volume":"9","author":"Hansen","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"2023032108374246700_jlb10861-cit-0015","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/annrheumdis-2018-213929","article-title":"Blockade of CD40\u2013CD154 pathway interactions suppresses ectopic lymphoid structures and inhibits pathology in the NOD\/ShiLtJ mouse model of Sj\u00f6gren\u2019s syndrome","volume":"78","author":"Wieczorek","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"2023032108374246700_jlb10861-cit-0016","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nm.2425","article-title":"Foxp3+ follicular regulatory T cells control the germinal center response","volume":"17","author":"Linterman","year":"2011","journal-title":"Nat Med"},{"key":"2023032108374246700_jlb10861-cit-0017","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.4049\/jimmunol.1101328","article-title":"Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells","volume":"187","author":"Wollenberg","year":"2011","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0018","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nm.2426","article-title":"Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions","volume":"17","author":"Chung","year":"2011","journal-title":"Nat Med."},{"key":"2023032108374246700_jlb10861-cit-0019","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1084\/jem.192.11.1545","article-title":"Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production","volume":"192","author":"Breitfeld","year":"2000","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0020","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1084\/jem.192.11.1553","article-title":"CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function","volume":"192","author":"Schaerli","year":"2000","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0021","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1084\/jem.193.12.1373","article-title":"Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells","volume":"193","author":"Kim","year":"2001","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0022","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/ni0901-876","article-title":"Separable effector T cell populations specialized for B cell help or tissue inflammation","volume":"2","author":"Campbell","year":"2001","journal-title":"Nat Immunol"},{"key":"2023032108374246700_jlb10861-cit-0023","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4049\/jimmunol.173.1.68","article-title":"T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1\/Th2 effector cells that provide help for B cells","volume":"173","author":"Chtanova","year":"2004","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0024","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1084\/jem.181.4.1293","article-title":"A subset of CD4+ memory T cells contains preformed CD40 ligand that is rapidly but transiently expressed on their surface after activation through the T cell receptor complex","volume":"181","author":"Casamayor-Palleja","year":"1995","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0025","doi-asserted-by":"crossref","first-page":"e20191638","DOI":"10.1084\/jem.20191638","article-title":"Regulation of the germinal center and humoral immunity by interleukin-21","volume":"217","author":"Tangye","year":"2020","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0026","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.4049\/jimmunol.175.4.2340","article-title":"The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo","volume":"175","author":"Akiba","year":"2005","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0027","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.4049\/jimmunol.177.7.4927","article-title":"ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells","volume":"177","author":"Bossaller","year":"2006","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0028","doi-asserted-by":"crossref","first-page":"E488","DOI":"10.1073\/pnas.1100898108","article-title":"Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers","volume":"108","author":"Bentebibel","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023032108374246700_jlb10861-cit-0029","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.1176676","article-title":"Bcl6 mediates the development of T follicular helper cells","volume":"325","author":"Nurieva","year":"2009","journal-title":"Science"},{"key":"2023032108374246700_jlb10861-cit-0030","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"2023032108374246700_jlb10861-cit-0031","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0032","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1084\/jem.20120994","article-title":"The origins, function, and regulation of T follicular helper cells","volume":"209","author":"Ma","year":"2012","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0033","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.immuni.2011.03.025","article-title":"Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity","volume":"34","author":"Kitano","year":"2011","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0034","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature12910","article-title":"Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development","volume":"507","author":"Liu","year":"2014","journal-title":"Nature"},{"key":"2023032108374246700_jlb10861-cit-0035","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1016\/j.ajpath.2019.08.008","article-title":"Achaete-scute homologue 2-regulated follicular helper T cells promote autoimmunity in a murine model for Sjogren syndrome","volume":"189","author":"Otsuka","year":"2019","journal-title":"Am J Pathol"},{"key":"2023032108374246700_jlb10861-cit-0036","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ni.2947","article-title":"The cytokine TGF-beta co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells","volume":"15","author":"Schmitt","year":"2014","journal-title":"Nat Immunol"},{"key":"2023032108374246700_jlb10861-cit-0037","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.immuni.2011.03.024","article-title":"Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone","volume":"34","author":"Kerfoot","year":"2011","journal-title":"Immunity"},{"issue":"Suppl 1","key":"2023032108374246700_jlb10861-cit-0038","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s10875-016-0268-3","article-title":"Human circulating T follicular helper cell subsets in health and disease","volume":"36","author":"Ueno","year":"2016","journal-title":"J Clin Immunol"},{"key":"2023032108374246700_jlb10861-cit-0039","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.it.2014.06.002","article-title":"Phenotype and functions of memory Tfh cells in human blood","volume":"35","author":"Schmitt","year":"2014","journal-title":"Trends Immunol"},{"key":"2023032108374246700_jlb10861-cit-0040","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.immuni.2013.09.007","article-title":"Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure","volume":"39","author":"He","year":"2013","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0041","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/art.25032","article-title":"Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus","volume":"62","author":"Simpson","year":"2010","journal-title":"Arthritis Rheum"},{"key":"2023032108374246700_jlb10861-cit-0042","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0043","doi-asserted-by":"crossref","first-page":"176ra132","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"Bentebibel","year":"2013","journal-title":"Sci Transl Med"},{"key":"2023032108374246700_jlb10861-cit-0044","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.immuni.2013.08.031","article-title":"Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses","volume":"39","author":"Locci","year":"2013","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0045","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.semarthrit.2012.07.003","article-title":"The role of ectopic germinal centers in the immunopathology of primary Sjogren\u2019s syndrome: a systematic review","volume":"42","author":"Risselada","year":"2013","journal-title":"Semin Arthritis Rheum"},{"key":"2023032108374246700_jlb10861-cit-0046","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"2023032108374246700_jlb10861-cit-0047","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.bbrc.2012.04.133","article-title":"Role of the frequency of blood CD4(+) CXCR5(+) CCR6(+) T cells in autoimmunity in patients with Sjogren\u2019s syndrome","volume":"422","author":"Li","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"2023032108374246700_jlb10861-cit-0048","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.clim.2013.02.024","article-title":"Follicular helper T cells may play an important role in the severity of primary Sjogren\u2019s syndrome","volume":"147","author":"Szabo","year":"2013","journal-title":"Clin Immunol"},{"key":"2023032108374246700_jlb10861-cit-0049","first-page":"1988","article-title":"CD4+CXCR5+ follicular helper T cells in salivary gland promote B cells maturation in patients with primary Sjogren\u2019s syndrome","volume":"7","author":"Jin","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"2023032108374246700_jlb10861-cit-0050","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/rheumatology\/keu316","article-title":"Umbilical cord mesenchymal stem cells inhibit the differentiation of circulating T follicular helper cells in patients with primary Sjogren\u2019s syndrome through the secretion of indoleamine 2,3-dioxygenase","volume":"54","author":"Liu","year":"2015","journal-title":"Rheumatology (Oxford)"},{"key":"2023032108374246700_jlb10861-cit-0051","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/cei.12703","article-title":"A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjogren\u2019s syndrome and systemic lupus erythematosus","volume":"183","author":"Szabo","year":"2016","journal-title":"Clin Exp Immunol"},{"key":"2023032108374246700_jlb10861-cit-0052","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1002\/art.40165","article-title":"Attenuation of follicular helper T cell-dependent B cell hyperactivity by abatacept treatment in primary Sjogren\u2019s syndrome","volume":"69","author":"Verstappen","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0053","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3899\/jrheum.160313","article-title":"B cell depletion therapy normalizes circulating follicular Th cells in primary Sjogren syndrome","volume":"44","author":"Verstappen","year":"2017","journal-title":"J Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0054","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/1573397113666170125122858","article-title":"Unique phenotypes and functions of follicular helper T cells and regulatory T cells in Sjogren\u2019s syndrome","volume":"14","author":"Saito","year":"2018","journal-title":"Curr Rheumatol Rev"},{"key":"2023032108374246700_jlb10861-cit-0055","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.4110\/in.2019.19.e26","article-title":"Circulating CCR7(lo)PD-1(hi) follicular helper T cells indicate disease activity and glandular inflammation in patients with primary Sjogren\u2019s syndrome","volume":"19","author":"Kim","year":"2019","journal-title":"Immune Netw"},{"key":"2023032108374246700_jlb10861-cit-0056","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/art.40488","article-title":"Is the T follicular regulatory:follicular helper T cell ratio in blood a biomarker for ectopic lymphoid structure formation in Sjogren\u2019s syndrome? Comment on the article by Fonseca et al","volume":"70","author":"Verstappen","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0057","doi-asserted-by":"crossref","first-page":"R179","DOI":"10.1186\/ar3504","article-title":"Impact of interleukin-21 in the pathogenesis of primary Sjogren\u2019s syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands","volume":"13","author":"Kang","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"2023032108374246700_jlb10861-cit-0058","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1365-2249.2012.04606.x","article-title":"Selective localization of T helper subsets in labial salivary glands from primary Sjogren\u2019s syndrome patients","volume":"169","author":"Maehara","year":"2012","journal-title":"Clin Exp Immunol"},{"key":"2023032108374246700_jlb10861-cit-0059","doi-asserted-by":"crossref","first-page":"631787","DOI":"10.1155\/2014\/631787","article-title":"The histopathology of labial salivary glands in primary Sjogren\u2019s syndrome: focusing on follicular helper T cells in the inflammatory infiltrates","volume":"2014","author":"Szabo","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2023032108374246700_jlb10861-cit-0060","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/art.40424","article-title":"The ratio of blood T follicular regulatory cells to T follicular helper cells marks ectopic lymphoid structure formation while activated follicular helper T cells indicate disease activity in primary Sjogren\u2019s syndrome","volume":"70","author":"Fonseca","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0061","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/rheumatology\/kez268","article-title":"Epigenetically quantified immune cells in salivary glands of Sjogren\u2019s syndrome patients: a novel tool that detects robust correlations of T follicular helper cells with immunopathology","volume":"59","author":"Blokland","year":"2020","journal-title":"Rheumatology (Oxford)"},{"key":"2023032108374246700_jlb10861-cit-0062","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/rheumatology\/ket434","article-title":"Follicular helper T cells in autoimmune diseases","volume":"53","author":"Papp","year":"2014","journal-title":"Rheumatology (Oxford)"},{"key":"2023032108374246700_jlb10861-cit-0063","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.immuni.2011.01.021","article-title":"A subset of interleukin-21+ chemokine receptor CCR9+ T helper cells target accessory organs of the digestive system in autoimmunity","volume":"34","author":"McGuire","year":"2011","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0064","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1002\/art.40182","article-title":"Increased CCL25 and T helper cells expressing CCR9 in the salivary glands of patients with primary Sjogren\u2019s syndrome: potential new axis in lymphoid neogenesis","volume":"69","author":"Blokland","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2023032108374246700_jlb10861-cit-0065","doi-asserted-by":"crossref","first-page":"e12852","DOI":"10.1111\/sji.12852","article-title":"Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjogren\u2019s syndrome to facilitate their concerted migration","volume":"91","author":"Blokland","year":"2020","journal-title":"Scand J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0066","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.4049\/jimmunol.1002828","article-title":"CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses","volume":"186","author":"Chevalier","year":"2011","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0067","doi-asserted-by":"crossref","first-page":"20371","DOI":"10.1073\/pnas.0911573106","article-title":"Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase","volume":"106","author":"Gigoux","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023032108374246700_jlb10861-cit-0068","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1016\/j.transproceed.2019.08.039","article-title":"Inhibition of T helper cell differentiation by tacrolimus or sirolimus results in reduced B-cell activation: effects on T follicular helper cells","volume":"51","author":"Kraaijeveld","year":"2019","journal-title":"Transplant Proc"},{"key":"2023032108374246700_jlb10861-cit-0069","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/cei.12604","article-title":"Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells","volume":"180","author":"De Bruyne","year":"2015","journal-title":"Clin Exp Immunol"},{"key":"2023032108374246700_jlb10861-cit-0070","doi-asserted-by":"crossref","first-page":"e51982","DOI":"10.1371\/journal.pone.0051982","article-title":"Inhibition of aberrant circulating Tfh cell proportions by corticosteroids in patients with systemic lupus erythematosus","volume":"7","author":"Feng","year":"2012","journal-title":"PLoS One"},{"key":"2023032108374246700_jlb10861-cit-0071","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.imlet.2017.07.010","article-title":"Achaete-scute complex homologue 2 accelerates the development of Sjogren\u2019s syndrome-like disease in the NOD\/ShiLtJ mouse","volume":"190","author":"Kim","year":"2017","journal-title":"Immunol Lett"},{"key":"2023032108374246700_jlb10861-cit-0072","doi-asserted-by":"crossref","first-page":"E6659","DOI":"10.1073\/pnas.1606646113","article-title":"miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity","volume":"113","author":"Serr","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023032108374246700_jlb10861-cit-0073","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ni.3054","article-title":"Pathophysiology of T follicular helper cells in humans and mice","volume":"16","author":"Ueno","year":"2015","journal-title":"Nat Immunol"},{"key":"2023032108374246700_jlb10861-cit-0074","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.4049\/jimmunol.1601687","article-title":"Disruption of pathogenic cellular networks by IL-21 blockade leads to disease amelioration in murine lupus","volume":"198","author":"Choi","year":"2017","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0075","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.jaci.2020.03.036","article-title":"Targeting ICOS expressed on CXCR5(+)PD-1(+) T helper cells suppresses the progression of pemphigus vulgaris","volume":"146","author":"Kim","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"2023032108374246700_jlb10861-cit-0076","doi-asserted-by":"crossref","first-page":"45.19","DOI":"10.4049\/jimmunol.200.Supp.45.19","article-title":"Selective inhibition of Tfh cells by a small molecule inhibitor abrogates progression of experimental inflammatory arthritis","volume":"200","author":"Zhang","year":"2018","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0077","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.immuni.2016.08.017","article-title":"mTORC1 and mTORC2 kinase signaling and glucose metabolism drive follicular helper T cell differentiation","volume":"45","author":"Zeng","year":"2016","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0078","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1182\/blood-2011-11-391144","article-title":"Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome","volume":"120","author":"Xu","year":"2012","journal-title":"Blood"},{"key":"2023032108374246700_jlb10861-cit-0079","doi-asserted-by":"crossref","first-page":"e1106","DOI":"10.1002\/cti2.1106","article-title":"Follicular regulatory T cells: a novel target for immunotherapy?","volume":"9","author":"Huang","year":"2020","journal-title":"Clin Transl Immunol"},{"key":"2023032108374246700_jlb10861-cit-0080","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1084\/jem.20130604","article-title":"Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression","volume":"211","author":"Vaeth","year":"2014","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0081","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1084\/jem.20170901","article-title":"Deficiency in T follicular regulatory cells promotes autoimmunity","volume":"215","author":"Fu","year":"2018","journal-title":"J Exp Med"},{"key":"2023032108374246700_jlb10861-cit-0082","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.3389\/fimmu.2018.01910","article-title":"Control of germinal center responses by T-follicular regulatory cells","volume":"9","author":"Wing","year":"2018","journal-title":"Front Immunol"},{"key":"2023032108374246700_jlb10861-cit-0083","doi-asserted-by":"crossref","first-page":"832","DOI":"10.4049\/jimmunol.1500759","article-title":"Circulating follicular regulatory T cells are defective in multiple sclerosis","volume":"195","author":"Dhaeze","year":"2015","journal-title":"J Immunol"},{"key":"2023032108374246700_jlb10861-cit-0084","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aan1487","article-title":"Human blood Tfr cells are indicators of ongoing humoral activity not fully licensed with suppressive function","volume":"2","author":"Fonseca","year":"2017","journal-title":"Sci Immunol"},{"key":"2023032108374246700_jlb10861-cit-0085","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.immuni.2014.02.005","article-title":"Transcription factor STAT3 and type I interferons are corepressive insulators for differentiation of follicular helper and T helper 1 cells","volume":"40","author":"Ray","year":"2014","journal-title":"Immunity"},{"key":"2023032108374246700_jlb10861-cit-0086","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13075-019-1904-0","article-title":"Metformin improves salivary gland inflammation and hypofunction in murine Sjogren\u2019s syndrome","volume":"21","author":"Kim","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"2023032108374246700_jlb10861-cit-0087","doi-asserted-by":"crossref","first-page":"109806","DOI":"10.1016\/j.biopha.2019.109806","article-title":"Catalpol ameliorates Sjogren\u2019s Syndrome by modulating interplay of T and B cells","volume":"123","author":"Lin","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"2023032108374246700_jlb10861-cit-0088","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.4110\/in.2019.19.e7","article-title":"Aged sanroque mice spontaneously develop Sjogren\u2019s syndrome-like disease","volume":"19","author":"Choi","year":"2019","journal-title":"Immune Netw"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.5MR1020-057RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.5MR1020-057RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/109\/2\/437\/49460075\/jlb10861.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/109\/2\/437\/49460075\/jlb10861.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T21:25:07Z","timestamp":1679433907000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/109\/2\/437\/6884590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":88,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,12,15]]},"published-print":{"date-parts":[[2021,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.5mr1020-057rr","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2]]},"published":{"date-parts":[[2020,12,15]]},"assertion":[{"value":"2020-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}