A study published in Science reveals that sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell (DC) axis. The research shows that androgens suppress the activity of type 2 innate lymphoid cells (ILC2), leading to reduced accumulation and activation of DCs in males, which in turn results in weaker skin immunity. This mechanism is further influenced by sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and the microbiota calibrating its tone. The study highlights that females have a higher accumulation of T cells in the skin at steady state and in response to the microbiota compared to males. The skin's immune system is regulated by male sex hormones acting on ILC2, which in turn control DC homeostasis. The research also demonstrates that ILC2 control cDC1 homeostasis in a GM-CSF-dependent manner, and that the microbiota further shapes sex-biased immune differences by enhancing type 17 programs. The findings suggest that the dual action of sex hormones and the microbiota defines tissue immune set-points, with sex hormones controlling the strength of local immunity and the microbiota calibrating its tone. The study provides insights into the mechanisms underlying immune sexual dimorphism and has implications for understanding disease etiology and tropism between males and females.A study published in Science reveals that sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell (DC) axis. The research shows that androgens suppress the activity of type 2 innate lymphoid cells (ILC2), leading to reduced accumulation and activation of DCs in males, which in turn results in weaker skin immunity. This mechanism is further influenced by sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and the microbiota calibrating its tone. The study highlights that females have a higher accumulation of T cells in the skin at steady state and in response to the microbiota compared to males. The skin's immune system is regulated by male sex hormones acting on ILC2, which in turn control DC homeostasis. The research also demonstrates that ILC2 control cDC1 homeostasis in a GM-CSF-dependent manner, and that the microbiota further shapes sex-biased immune differences by enhancing type 17 programs. The findings suggest that the dual action of sex hormones and the microbiota defines tissue immune set-points, with sex hormones controlling the strength of local immunity and the microbiota calibrating its tone. The study provides insights into the mechanisms underlying immune sexual dimorphism and has implications for understanding disease etiology and tropism between males and females.