{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:36:10Z","timestamp":1793507770356,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EJPRD\/0003\/2019"],"award-info":[{"award-number":["EJPRD\/0003\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EJPRD\/0003\/2019"],"award-info":[{"award-number":["EJPRD\/0003\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EJPRD\/0003\/2019"],"award-info":[{"award-number":["EJPRD\/0003\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EJPRD\/0003\/2019"],"award-info":[{"award-number":["EJPRD\/0003\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EJPRD\/0003\/2019"],"award-info":[{"award-number":["EJPRD\/0003\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["EJPRD\/0003\/2019"],"award-info":[{"award-number":["EJPRD\/0003\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto\u2019s thyroiditis (HT, n\u2009=\u200918), rheumatoid arthritis (RA, n\u2009=\u200916), or systemic lupus erythematosus (SLE, n\u2009=\u200932), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells (<jats:italic>p<\/jats:italic>\u2009=\u20090.0215) and a reduced Tfr\/Tfh ratio (<jats:italic>p<\/jats:italic>\u2009=\u20090.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh (<jats:italic>p<\/jats:italic>\u2009=\u20090.0494 and <jats:italic>p<\/jats:italic>\u2009=\u20090.0392, respectively) and Tfr (<jats:italic>p<\/jats:italic>\u2009=\u20090.0003 and <jats:italic>p<\/jats:italic>\u2009=\u20090.0001, respectively) cells, resulting in an unchanged Tfr\/Tfh ratio. Activated PD-1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup>Tfh and CD4<jats:sup>+<\/jats:sup>PD-1<jats:sup>+<\/jats:sup>CXCR5<jats:sup>\u2013<\/jats:sup>Tph cells were raised only in patients with SLE (<jats:italic>p<\/jats:italic>\u2009=\u20090.0022 and <jats:italic>p<\/jats:italic>\u2009=\u20090.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification.<\/jats:p>","DOI":"10.1038\/s41598-022-21576-8","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T10:03:36Z","timestamp":1666346616000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation"],"prefix":"10.1038","volume":"12","author":[{"given":"Filipa","family":"Ribeiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasco C.","family":"Rom\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1tia","family":"Jesus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"\u00c1gua-Doce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia C.","family":"Barreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana Lopes","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ema","family":"Nobre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jo\u00e3o","family":"Bugalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e1lter R.","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Eurico Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Graca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"21576_CR1","doi-asserted-by":"publisher","first-page":"5191","DOI":"10.1172\/JCI76861","volume":"124","author":"PT Sage","year":"2014","unstructured":"Sage, P. T., Alvarez, D., Godec, J., Von Andrian, U. H. & Sharpe, A. H. Circulating T follicular regulatory and helper cells have memory-like properties. J. Clin. Invest. 124, 5191\u20135204 (2014).","journal-title":"J. Clin. Invest."},{"key":"21576_CR2","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.it.2014.06.002","volume":"35","author":"N Schmitt","year":"2014","unstructured":"Schmitt, N., Bentebibel, S. E. & Ueno, H. Phenotype and functions of memory Tfh cells in human blood. Trends Immunol. 35, 436\u2013442 (2014).","journal-title":"Trends Immunol."},{"key":"21576_CR3","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","volume":"34","author":"R Morita","year":"2011","unstructured":"Morita, R. et al. Human blood CXCR5+CD4+ T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34, 108\u2013121 (2011).","journal-title":"Immunity"},{"key":"21576_CR4","first-page":"1","volume":"1487","author":"VR Fonseca","year":"2017","unstructured":"Fonseca, V. R. et al. Human blood Tfr cells are indicators of ongoing humoral activity not fully licensed with suppressive function. Sci. Immunol. 1487, 1\u201313 (2017).","journal-title":"Sci. Immunol."},{"key":"21576_CR5","doi-asserted-by":"publisher","first-page":"4553","DOI":"10.4049\/jimmunol.1101328","volume":"187","author":"I Wollenberg","year":"2011","unstructured":"Wollenberg, I. et al. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J. Immunol. 187, 4553\u20134560 (2011).","journal-title":"J. Immunol."},{"key":"21576_CR6","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/nm.2426","volume":"17","author":"Y Chung","year":"2011","unstructured":"Chung, Y. et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat. Med. 17, 983\u2013988 (2011).","journal-title":"Nat. Med."},{"key":"21576_CR7","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1038\/nm.2425","volume":"17","author":"MA Linterman","year":"2011","unstructured":"Linterman, M. A. et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 17, 975\u2013982 (2011).","journal-title":"Nat. Med."},{"key":"21576_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms15067","volume":"8","author":"AR Maceiras","year":"2017","unstructured":"Maceiras, A. R. et al. T follicular helper and T follicular regulatory cells have different TCR specificity. Nat. Commun. 8, 1\u201312 (2017).","journal-title":"Nat. Commun."},{"key":"21576_CR9","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1038\/ni.3578","volume":"17","author":"PT Sage","year":"2016","unstructured":"Sage, P. T. et al. Suppression by Tfr cells leads to durable and selective inhibition of B cell effector function. Nat. Immunol. 17, 1436\u20131446 (2016).","journal-title":"Nat. Immunol."},{"key":"21576_CR10","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.immuni.2014.12.006","volume":"41","author":"JB Wing","year":"2014","unstructured":"Wing, J. B., Ise, W., Kurosaki, T. & Sakaguchi, S. Regulatory T cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4. Immunity 41, 1013\u20131025 (2014).","journal-title":"Immunity"},{"key":"21576_CR11","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1084\/jem.20130604","volume":"211","author":"M Vaeth","year":"2014","unstructured":"Vaeth, M. et al. Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression. J. Exp. Med. 211, 545\u2013561 (2014).","journal-title":"J. Exp. Med."},{"key":"21576_CR12","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1084\/jem.20170901","volume":"215","author":"W Fu","year":"2018","unstructured":"Fu, W. et al. Deficiency in T follicular regulatory cells promotes autoimmunity. J. Exp. Med. 215, 815\u2013825 (2018).","journal-title":"J. Exp. Med."},{"key":"21576_CR13","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.it.2015.05.005","volume":"36","author":"PT Sage","year":"2015","unstructured":"Sage, P. T. & Sharpe, A. H. T follicular regulatory cells in the regulation of B cell responses. Trends Immunol. 36, 410\u2013418 (2015).","journal-title":"Trends Immunol."},{"key":"21576_CR14","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1002\/art.40424","volume":"70","author":"VR Fonseca","year":"2018","unstructured":"Fonseca, V. R. et al. 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 Sj\u00f6gren\u2019s Syndrome. Arthritis Rheumatol. 70, 774\u2013784 (2018).","journal-title":"Arthritis Rheumatol."},{"key":"21576_CR15","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1002\/art.40488","volume":"70","author":"GM Verstappen","year":"2018","unstructured":"Verstappen, G. M. et al. Is the T follicular regulatory:follicular helper T cell ratio in blood a biomarker for ectopic lymphoid structure formation in Sj\u00f6gren\u2019s Syndrome? Comment on the article by Fonseca et al.. Arthritis Rheumatol. 70, 1354\u20131355. https:\/\/doi.org\/10.1002\/art.40488 (2018).","journal-title":"Arthritis Rheumatol."},{"key":"21576_CR16","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/cei.13118","volume":"192","author":"LA Aqrawi","year":"2018","unstructured":"Aqrawi, L. A. et al. Diminished CXCR5 expression in peripheral blood of patients with Sj\u00f6gren\u2019s syndrome may relate to both genotype and salivary gland homing. Clin. Exp. Immunol. 192, 259\u2013270 (2018).","journal-title":"Clin. Exp. Immunol."},{"key":"21576_CR17","doi-asserted-by":"publisher","first-page":"832","DOI":"10.4049\/jimmunol.1500759","volume":"195","author":"T Dhaeze","year":"2015","unstructured":"Dhaeze, T. et al. Circulating follicular regulatory T cells are defective in multiple sclerosis. J. Immunol. 195, 832\u2013840 (2015).","journal-title":"J. Immunol."},{"key":"21576_CR18","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.clim.2017.07.004","volume":"183","author":"B Xu","year":"2017","unstructured":"Xu, B. et al. The ratio of circulating follicular T helper cell to follicular T regulatory cell is correlated with disease activity in systemic lupus erythematosus. Clin. Immunol. 183, 46\u201353 (2017).","journal-title":"Clin. Immunol."},{"key":"21576_CR19","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/1440-1681.12330","volume":"42","author":"Y Shan","year":"2015","unstructured":"Shan, Y. et al. Higher frequency of peripheral blood follicular regulatory T cells in patients with new onset ankylosing spondylitis. Clin. Exp. Pharmacol. Physiol. 42, 154\u2013161 (2015).","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"21576_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/sciimmunol.abd8411","volume":"6","author":"S Kumar","year":"2021","unstructured":"Kumar, S. et al. Developmental bifurcation of human T follicular regulatory cells. Sci. Immunol. 6, 1\u201315 (2021).","journal-title":"Sci. Immunol."},{"key":"21576_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/imm.12774","volume":"152","author":"AR Maceiras","year":"2017","unstructured":"Maceiras, A. R., Fonseca, V. R., Agua-Doce, A. & Graca, L. T follicular regulatory cells in mice and men. Immunology 152, 25\u201335 (2017).","journal-title":"Immunology"},{"key":"21576_CR22","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1038\/ni.3837","volume":"18","author":"D Botta","year":"2017","unstructured":"Botta, D. et al. Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection. Nat. Immunol. 18, 1249\u20131260 (2017).","journal-title":"Nat. Immunol."},{"key":"21576_CR23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/imr.12739","volume":"288","author":"VR Fonseca","year":"2019","unstructured":"Fonseca, V. R., Ribeiro, F. & Graca, L. T follicular regulatory (Tfr ) cells: Dissecting the complexity of cell compartments. Immunol. Rev. 288, 112\u2013127 (2019).","journal-title":"Immunol. Rev."},{"key":"21576_CR24","doi-asserted-by":"publisher","first-page":"E6400","DOI":"10.1073\/pnas.1705551114","volume":"114","author":"JB Wing","year":"2017","unstructured":"Wing, J. B. et al. A distinct subpopulation of CD25(-) T follicular regulatory cells localizes in the germinal centers. Proc. Natl. Acad. Sci. U S A 114, E6400\u2013E6409 (2017).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"21576_CR25","doi-asserted-by":"publisher","first-page":"eaan0368","DOI":"10.1126\/sciimmunol.aan0368","volume":"2","author":"P-GG Ritvo","year":"2017","unstructured":"Ritvo, P.-G.G. et al. Tfr cells lack IL-2R\u03b1 but express decoy IL-1R2 and IL-1Ra and suppress the IL-1\u2013dependent activation of Tfh cells. Sci. Immunol. 2, eaan0368 (2017).","journal-title":"Sci. Immunol."},{"key":"21576_CR26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s10238-018-0530-5","volume":"19","author":"X Wang","year":"2019","unstructured":"Wang, X. et al. Imbalance of circulating Tfr\/Tfh ratio in patients with rheumatoid arthritis. Clin. Exp. Med. 19, 55\u201364 (2019).","journal-title":"Clin. Exp. Med."},{"key":"21576_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.01226","volume":"9","author":"J Deng","year":"2018","unstructured":"Deng, J. et al. Signal transducer and activator of transcription 3 hyperactivation associates with follicular helper T cell differentiation and disease activity in rheumatoid arthritis. Front. Immunol. 9, 1\u201311 (2018).","journal-title":"Front. Immunol."},{"key":"21576_CR28","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1002\/art.40586","volume":"70","author":"VC Rom\u00e3o","year":"2018","unstructured":"Rom\u00e3o, V. C., Fonseca, J. E., Agua-Doce, A. & Graca, L. T follicular regulatory cells are decreased in patients with established treated rheumatoid arthritis with active disease: Comment on the article by Liu et al.. Arthritis Rheumatol. 70, 1893\u20131895 (2018).","journal-title":"Arthritis Rheumatol."},{"key":"21576_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scitranslmed.3005191","volume":"5","author":"SE Bentebibel","year":"2013","unstructured":"Bentebibel, S. E. et al. Induction of ICOS+CXCR3+CXCR5+ T H cells correlates with antibody responses to influenza vaccination. Sci. Transl. Med. 5, 1\u201311 (2013).","journal-title":"Sci. Transl. Med."},{"key":"21576_CR30","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.vaccine.2016.11.059","volume":"35","author":"MA Pilkinton","year":"2017","unstructured":"Pilkinton, M. A. et al. Greater activation of peripheral T follicular helper cells following high dose influenza vaccine in older adults forecasts seroconversion. Vaccine 35, 329\u2013336 (2017).","journal-title":"Vaccine"},{"key":"21576_CR31","doi-asserted-by":"publisher","first-page":"eaag2152","DOI":"10.1126\/sciimmunol.aag2152","volume":"2","author":"RS Herati","year":"2017","unstructured":"Herati, R. S. et al. Successive annual influenza vaccination induces a recurrent oligoclonotypic memory response in circulating T follicular helper cells. Sci. Immunol. 2, eaag2152 (2017).","journal-title":"Sci. Immunol."},{"key":"21576_CR32","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.3389\/fimmu.2018.01924","volume":"9","author":"DA Rao","year":"2018","unstructured":"Rao, D. A. T cells that help B cells in chronically inflamed tissues. Front. Immunol. 9, 1924 (2018).","journal-title":"Front. Immunol."},{"key":"21576_CR33","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/s41423-020-00529-z","volume":"18","author":"H Yoshitomi","year":"2021","unstructured":"Yoshitomi, H. & Ueno, H. Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases. Cell. Mol. Immunol. 18, 523\u2013527 (2021).","journal-title":"Cell. Mol. Immunol."},{"key":"21576_CR34","doi-asserted-by":"publisher","first-page":"e130062","DOI":"10.1172\/jci.insight.130062","volume":"4","author":"AV Bocharnikov","year":"2019","unstructured":"Bocharnikov, A. V. et al. PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI Insight 4, e130062 (2019).","journal-title":"JCI Insight"},{"key":"21576_CR35","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1093\/rheumatology\/kez228","volume":"58","author":"J Lin","year":"2019","unstructured":"Lin, J., Yu, Y., Ma, J., Ren, C. & Chen, W. PD-1+CXCR5-CD4+T cells are correlated with the severity of systemic lupus erythematosus. Rheumatology 58, 2188\u20132192 (2019).","journal-title":"Rheumatology"},{"key":"21576_CR36","first-page":"1861","volume":"58","author":"A Makiyama","year":"2019","unstructured":"Makiyama, A. et al. Expanded circulating peripheral helper T cells in systemic lupus erythematosus: Association with disease activity and B cell differentiation. Rheumatology 58, 1861\u20131869 (2019).","journal-title":"Rheumatology"},{"key":"21576_CR37","doi-asserted-by":"publisher","first-page":"R104","DOI":"10.1186\/ar4553","volume":"16","author":"M Bonelli","year":"2014","unstructured":"Bonelli, M. et al. CD4+CD25-Foxp3+ T cells: A marker for lupus nephritis?. Arthritis Res. Ther. 16, R104 (2014).","journal-title":"Arthritis Res. Ther."},{"key":"21576_CR38","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.3389\/fimmu.2018.01910","volume":"9","author":"JB Wing","year":"2018","unstructured":"Wing, J. B., Tekg\u00fc\u00e7, M. & Sakaguchi, S. Control of germinal center responses by T follicular regulatory cells. Front. Immunol. 9, 1910 (2018).","journal-title":"Front. Immunol."},{"key":"21576_CR39","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev-immunol-041015-055605","volume":"34","author":"CG Vinuesa","year":"2016","unstructured":"Vinuesa, C. G., Linterman, M. A., Yu, D. & MacLennan, I. C. M. Follicular helper T cells. Annu. Rev. Immunol. 34, 335\u2013368 (2016).","journal-title":"Annu. Rev. Immunol."},{"key":"21576_CR40","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.acthis.2013.10.009","volume":"116","author":"Y Chu","year":"2014","unstructured":"Chu, Y., Wang, F., Zhou, M., Chen, L. & Lu, Y. A preliminary study on the characterization of follicular helper T (Tfh) cells in rheumatoid arthritis synovium. Acta Histochem. 116, 539\u2013543 (2014).","journal-title":"Acta Histochem."},{"key":"21576_CR41","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature20810","volume":"542","author":"DA Rao","year":"2017","unstructured":"Rao, D. A. et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 542, 110\u2013114 (2017).","journal-title":"Nature"},{"key":"21576_CR42","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3389\/fimmu.2016.00430","volume":"7","author":"E Corsiero","year":"2016","unstructured":"Corsiero, E., Nerviani, A., Bombardieri, M. & Pitzalis, C. Ectopic lymphoid structures: Powerhouse of autoimmunity. Front. Immunol. 7, 430 (2016).","journal-title":"Front. Immunol."},{"key":"21576_CR43","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nrrheum.2015.141","volume":"11","author":"JH Duarte","year":"2015","unstructured":"Duarte, J. H. Hitting the brakes on ectopic lymphoid structure formation. Nat. Rev. Rheumatol. 11, 621\u2013621 (2015).","journal-title":"Nat. Rev. Rheumatol."},{"key":"21576_CR44","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.2174\/138920112802273209","volume":"13","author":"M Bombardieri","year":"2012","unstructured":"Bombardieri, M. & Pitzalis, C. Ectopic lymphoid neogenesis and lymphoid chemokines in Sjogren\u2019s Syndrome: at the interplay between chronic inflammation, autoimmunity and lymphomagenesis. Curr. Pharm. Biotechnol. 13, 1989\u20131996 (2012).","journal-title":"Curr. Pharm. Biotechnol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-21576-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-21576-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-21576-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T14:25:52Z","timestamp":1666448752000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-21576-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,21]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["21576"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-21576-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,21]]},"assertion":[{"value":"21 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17638"}}