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

• 成果类型: Article
• 署名作者: Chi, Liang; Liu, Can; Gribonika, Inta; Gschwend, Julia; Corral, Dan; Han, Seong-Ji; Lim, Ai Ing; Rivera, Claudia A.; Link, Verena M.; Wells, Alexandria C.; Bouladoux, Nicolas; Collins, Nicholas; Lima-Junior, Djalma S.; Enamorado, Michel; Rehermann, Barbara; Laffont, Sophie; Guery, Jean-Charles; Tussiwand, Roxane; Schneider, Christoph; Belkaid, Yasmine
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Zurich; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Institut National de la Sante et de la Recherche Medicale (Inserm); National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13247
• DOI: 10.1126/science.adk6200
• 发表日期: 2024-04-12
• 关键词: population-based incidence; langerhans cells; dendritic cells; olmsted county; microbiota; GENDER; mice; differentiation; inflammation; carcinoma

摘要

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.