Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

L Chi, C Liu, I Gribonika, J Gschwend, D Corral, SJ Han… - Science, 2024 - science.org
L Chi, C Liu, I Gribonika, J Gschwend, D Corral, SJ Han, AI Lim, CA Rivera, VM Link
Science, 2024science.org
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 uncovered a dominant role for type 2 innate lymphoid cells
(ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative
regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and
activation in males, along with reduced tissue immunity. Collectively, our results reveal a …
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 uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell 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.
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