Female hormones enhance skin T cell expansion and suppress IFN-γ production
- 1Lydia Becker Institute of Immunology, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester , ,
- 2Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, The University of Manchester and Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre , ,
- 3No7 Beauty Company, The Boots Group , ,
Abstract
Introduction: Estrogen receptors (ERs) regulate immune function, but their expression across immune cell subsets and hormone responsiveness in human skin are not fully understood.
Methods: We used 10-color flow cytometry to quantify ER (ERα, ERβ, 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.
Results: ERα was predominantly expressed on the membrane of NK and NKT cells, while ERβ was mainly intracellular and showed low expression across subsets. GPER1 displayed a similar membrane distribution to ERα but at lower expression levels. T cells displayed moderate membrane ERα 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. In vitro , female hormones dose-dependently decreased IFN-γ production in T and NK cells but did not alter cytotoxic mediator production in these cells.
Conclusions: 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-γ, 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.
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BibTeX
@article{bahri2026female,
title = {{Female hormones enhance skin T cell expansion and suppress IFN-γ production}},
author = {Rajia Bahri and Chiara Tontini and Orsolya Kiss and Abigail K. Langton and Victoria L. Newton and Mike Bell and Silvia Bulfone-Paus},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1903552},
url = {https://europepmc.org/article/PMC/PMC13668513},
note = {CC BY},
}
RIS
TY - JOUR
TI - Female hormones enhance skin T cell expansion and suppress IFN-γ production
AU - Rajia Bahri
AU - Chiara Tontini
AU - Orsolya Kiss
AU - Abigail K. Langton
AU - Victoria L. Newton
AU - Mike Bell
AU - Silvia Bulfone-Paus
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1903552
UR - https://europepmc.org/article/PMC/PMC13668513
AB - Introduction: Estrogen receptors (ERs) regulate immune function, but their expression across immune cell subsets and hormone responsiveness in human skin are not fully understood. Methods: We used 10-color flow cytometry to quantify ER (ERα, ERβ, 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. Results: ERα was predominantly expressed on the membrane of NK and NKT cells, while ERβ was mainly intracellular and showed low expression across subsets. GPER1 displayed a similar membrane distribution to ERα but at lower expression levels. T cells displayed moderate membrane ERα 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. In vitro , female hormones dose-dependently decreased IFN-γ production in T and NK cells but did not alter cytotoxic mediator production in these cells. Conclusions: 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-γ, 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.
SN - 1664-3224
ER -