Menstrual cycle matters: How hormonal fluctuations could impact skin immunity in health and disease

Summary: Our study explores the relationship between hormonal changes during the menstrual cycle and their effects on skin health, focusing on Hidradenitis Suppurativa (HS) and healthy individuals. To study the effects of cyclic hormonal changes on the skin, we collected site-matched healthy-donor skin from five healthy women, and lesional and non-lesional skin from ten women with HS during the early follicular and luteal phases of the menstrual cycle. We used RNA-sequencing to identify differentially expressed genes between these phases that met the significance criteria (FDR < 0.05 and log2fold-change > 1.5). In healthy-donor skin, several upregulated genes, were involved in suppressing T cell and lymphocyte proliferation and activation, inhibiting cytokine-mediated signaling, and promoting regulatory T cell differentiation during the early follicular phase compared to the luteal phase as indicated by gene ontology (GO) overrepresentation analysis. In contrast, lesional HS skin showed a different set of upregulated genes related to innate immunity, microbial defense responses, and humoral responses during the early follicular phase compared to the luteal phase by GO terms. In non-lesional skin, no genes met the same significance criteria. Notably, the immunoregulatory pathways upregulated in healthy skin during the early follicular phase were not similarly activated in HS skin. While validation is ongoing, our transcriptome data suggest that the failure to activate immune regulatory pathways in HS may contribute to increased severity of skin lesions during the early follicular phase of the menstrual cycle. Our findings have implications for clinical trial design and insights into identifying new therapeutic targets for hormone-mediated inflammatory pathways in skin. Tarannum Jaleel¹, Dmitri Kazmin², Jade J. Lewis¹, Negar Foolad¹, Russell Hall¹, Andrea Coviello³, Donald McDonnell⁴, Jennifer Zhang^{1, 5} 1. Dermatology, Duke University School of Medicine, Durham, NC, United States. 2. Stanford University, Stanford, CA, United States. 3. Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 4. Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, United States. 5. Pathology, Duke University School of Medicine, Durham, NC, United States. Translational Studies: Preclinical