{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:11:39Z","timestamp":1777961499155,"version":"3.51.4"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      An adverse female bias exists across many autoimmune disorders, yet its underlying mechanisms, particularly the role of sex hormones, remain poorly understood. Furthermore, the physiological influence of sex hormones in regulating T cell function remains undefined. We examined the role of estrogen and progesterone, in modulating CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses, specifically with respect to inflammation and bone erosion associated markers in RA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Inflammatory markers, circulating antibodies, sex hormone receptors, ER\u03b1 and PR levels were investigated in both RA patients and controls. Further, RA CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were stimulated in varying concentrations of estradiol and progesterone and assessed for modulation in cytokines, transcription factors, RANKL, and FasL expression. Subsequent\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      studies were performed to examine the role of sex hormones in modulating T cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RA patients displayed systemic inflammation and high circulating antibodies, with significantly higher expression in synovial fluid. Higher expression of ER\u03b1 and PR was evinced on RA CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Upon hormone stimulation, patients displayed heterogeneous responses and were categorized into responders and non-responders based on modulation of cytokines, transcription factors, RANKL, and FasL expression. Our\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      Th1 and Th17 cells further suggested a role for sex hormones in modulating inflammatory responses under controlled conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest a potential role of sex hormones in modulating TCR responses, with possible implications for inflammatory pathways and bone erosion associated markers. Further studies are required to elucidate the underlying mechanisms and to evaluate their potential relevance for therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1813310","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:31:43Z","timestamp":1777959103000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Estrogen and progesterone-mediated differential modulation of CD4+ T-cell pathogenicity in rheumatoid arthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Rohila","family":"Jha","sequence":"first","affiliation":[{"name":"Biotechnology Research and Innovation Council (BRIC)- Institute of Life Sciences (ILS)","place":["Bhubaneswar, Odisha, India"]},{"name":"Regional Center for Biotechnology (RCB)","place":["Faridabad, Haryana, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubham 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