{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:24:45Z","timestamp":1792448685589,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871709, 81974549"],"award-info":[{"award-number":["81871709, 81974549"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by multiple autoantibodies, resulting in multiple organ and tissue damages. These pathogenic autoantibodies produced by B cells are closely correlated with follicular helper T (Tfh) cell subsets that play a fundamental role in the pathogenesis of SLE. The aim of the present study was to study the phenotype and role of circulating Tfh (cTfh) cell subsets and associated B cell subpopulations in active and inactive SLE patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty SLE outpatients and 24 healthy controls (HCs) were enrolled in this study. The frequency of cTfh cell and B cell subsets in peripheral blood mononuclear cells (PBMCs) and the plasma levels of eight cytokines were determined by flow cytometry, and plasma IL-21 levels were measured by ELISA. Meanwhile, we used MRL\/lpr mice as the model of SLE to research the alterations of Tfh cells in the thymus and spleen of mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Frequencies of CD4<jats:sup>+<\/jats:sup>CXCR5<jats:sup>+<\/jats:sup>CD45RA<jats:sup>-<\/jats:sup>effector cTfh cells, PD1<jats:sup>+<\/jats:sup>cTfh, PD1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup>cTfh, PD1<jats:sup>+<\/jats:sup>cTfh1, PD1<jats:sup>+<\/jats:sup>cTfh2, PD1<jats:sup>+<\/jats:sup>cTfh17, and PD1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup>cTfh1 cells as well as plasmablasts showed significant differences among HC, active and inactive SLE patients. Moreover, cytokines typically associated with cTfh cells, including IL-6 and IL-21, were elevated in active SLE patients compared to inactive SLE patients and HCs. Additionally, a positive correlation was observed between PD1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup> cTfh or PD1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup> cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1<jats:sup>+<\/jats:sup>ICOS<jats:sup>+<\/jats:sup> Tfh cells expansion in both thymus and spleen of MRL\/lpr mice, accompanied by increased frequencies in B cells and plasmablasts, meanwhile, cTfh1which expressing IFN-\u03b3 was increased in the peripheral blood of MRL\/lpr mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.928359","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T04:35:05Z","timestamp":1662093305000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":43,"title":["Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus 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