Sexual dimorphism in skin immunity is mediated by androgen-ILC2-dendritic cell axis [Bulk RNA-seq]

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncover a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. Collectively, this work uncovers an androgen-ILC2-DC axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set-points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.