Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2024 Apr 12;384(6692):eadk6200. doi: 10.1126/science.adk6200.
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.
男性和女性在免疫反应和疾病易感性方面存在显著差异。然而，导致组织免疫性别差异的因素仍知之甚少。在这里，我们发现 2 型先天淋巴样细胞（ILC2）在塑造皮肤组织免疫性别二态性方面起着主导作用。从机制上讲，雄激素对 ILC2 的负调控导致男性树突状细胞的积累和激活减少，组织免疫力降低。总的来说，我们的结果揭示了雄激素-ILC2-树突状细胞轴在控制组织免疫性别二态性中的作用。此外，这项工作表明，组织免疫设定点是由性激素和微生物群的双重作用决定的，其中性激素控制局部免疫的强度，而微生物群则调节其基调。
