Regulation of immune cell populations and immune pathways by sex hormones

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Immune responses differ between females and males. Females mount stronger immune responses against pathogens, vaccines, and malignancies. Enhanced immune responsiveness in females, however, comes at a cost, including significantly higher incidences of autoimmune diseases. Despite these well-established sex differences in malignancies, infectious and autoimmune diseases, the underlying biological mechanisms have not been systematically examined. Increasing evidence suggests that common biological pathways regulating immune cell functions are involved in sex-specific differences in immunity, and that these immune pathways can be regulated by sex hormones. The principal aim of the current proposal is to determine the impact of sex hormones on immune cells and pathways, testing the hypothesis that testosterone regulates inflammatory immune responses. We will use an integrated approach combining longitudinal samples from a human transgender cohort (hTGC) and mouse models to determine the impact of sex hormones on inflammatory pathways in innate and adaptive immune cells, using single cell multiomics NGS approaches.