Sexual dimorphism in skin immunity is mediated by androgen-ILC2-dendritic cell axis [scRNA-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. 5' single cell RNA-seq from T cells and dendritic cells from male and female mice following control or S. epidermidis treatment. Different treatments were labeled using BioLegend TotalSeq antibodies. DC and T cell libraries were loaded on two 10X Genomics lanes (lane1 and lane2).