FP12 Hormonal regulation of lymphoid immune dynamics in skin inflammation: differential oestrogen receptor expression and menopausal influences
Rajia Bahri, Rosie Gaskell, Orsolya Kiss, Abigail Langton, Victoria Newton, Mike Bell, Silvia Bulfone-PausAbstract
Introduction and aims
Menopause induces hormonal alterations in women, notably a reduction in oestrogen levels, which can compromise the immune system and elevate the risk of inflammation. This study sought to characterize oestrogen receptor expression in peripheral blood mononuclear cells (PBMCs) and examine the impact of menopausal status and hormone replacement therapy (HRT) on lymphoid immune responses in the skin following sodium lauryl sulfate (SLS)-induced irritation.
Methods
PBMCs were isolated from five healthy donors and evaluated for oestrogen receptor (ER) expression (ERα, ERβ and GPER1), both intracellularly and on cell membranes, using flow cytometry. Skin biopsies from pre- (n = 8) and postmenopausal women, with (n = 7) and without HRT (n = 9), were analysed through immunohistochemistry to assess T-cell, natural killer (NK) and NKT-cell populations and ERα expression before and after a 72-h SLS challenge. PBMCs were stimulated in vitro with female hormone cocktails containing dehydroepiandrosterone, progesterone, and oestrogen to assess cytokine [interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF)] and granzyme B production via flow cytometry.
Results
ERα was the predominant oestrogen receptor, with the highest membrane expression observed on NKT and NK cells, followed by T cells. Intracellular ERα expression was elevated across all cell types. ERβ and GPER1 exhibited minimal surface expression. In the skin, T-cell numbers increased significantly post-SLS in both pre- and postmenopausal women receiving HRT (P = 0.006), while NKT cells increased only in premenopausal women (P = 0.01), and NK cells remained unchanged. In vitro, female hormones dose-dependently inhibited T-cell production of GM-CSF and IFN-γ, without affecting granzyme B.
Conclusions
Oestrogen receptors are abundantly expressed on specific immune cells. Menopausal status and hormone replacement therapy differentially influence T and NK cell populations during skin inflammation, with premenopausal hormone levels playing a crucial role in regulating excessive inflammation. Consequently, reductions in female hormone levels may specifically affect certain immune cell populations, potentially compromising immune function.