{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:00:17Z","timestamp":1790830817652,"version":"4.1.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000770","name":"University of Manchester","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000770","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Estrogen receptors (ERs) regulate immune function, but their expression across immune cell subsets and hormone responsiveness in human skin are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used 10-color flow cytometry to quantify ER (ER\u03b1, ER\u03b2, and GPER1) expression in peripheral blood mononuclear cells (PBMCs) from healthy donors. We analyzed sex hormone gene expression using public single-cell RNA datasets. Skin immune responses to sodium lauryl sulfate (SLS) were assessed in pre- and post-menopausal women, with or without hormone replacement therapy (HRT). Furthermore, we measured the production of mediators in the ER expressing immune cytotoxic cells, specifically T and NK cells, in response to pre- and post-menopausal hormone cocktails.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ER\u03b1 was predominantly expressed on the membrane of NK and NKT cells, while ER\u03b2 was mainly intracellular and showed low expression across subsets. GPER1 displayed a similar membrane distribution to ER\u03b1 but at lower expression levels. T cells displayed moderate membrane ER\u03b1 and lower GPER1 expression. Gene expression analysis in women revealed strong ESR1 and ESR2 expression in T cells. In inflamed skin, HRT selectively increased T cell numbers after SLS exposure in post-menopausal women.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , female hormones dose-dependently decreased IFN-\u03b3 production in T and NK cells but did not alter cytotoxic mediator production in these cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ER expression levels and localization vary by immune cell subset, indicating that estrogen modulates immune responses in a cell-specific manner. Sex hormones differentially impact T and NK cell populations during skin inflammation, by increasing T cell numbers and, reducing IFN-\u03b3, without altering cytotoxic activity. These findings demonstrate that female sex hormones significantly influence immune responses in inflamed and aging skin and may guide the development of targeted therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1903552","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:46:59Z","timestamp":1790830019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Female hormones enhance skin T cell expansion and suppress IFN-\u03b3 production"],"prefix":"10.3389","volume":"17","author":[{"given":"Rajia","family":"Bahri","sequence":"first","affiliation":[{"name":"Lydia Becker Institute of Immunology, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester","place":["Manchester, United Kingdom"]},{"name":"Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of 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