Sex-specific adipose tissue imprinting of regulatory T cells (ATAC-seq)

Visceral adipose tissue (VAT) is a metabolically active endocrine organ that plays a critical role regulating organismal metabolism. Regulatory T (Treg) cells restrain VAT inflammation, and preserve insulin sensitivity and organismal metabolism. Here we report pronounced sexual dimorphism in VAT Treg cells, which were enriched specifically in males and differed strikingly from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. These differences were imprinted by the adipose tissue in a manner dependent on sex hormones. Male VAT was characterized by heightened inflammation, which resulted in CCR2-dependent recruitment of Treg cells. Sex hormones also regulated the differentiation of unique IL-33-producing stromal cell populations specific to the male VAT, which paralleled the local expansion of Treg cells and the induction of a transcriptional program controlled by transcription factor Blimp1. Overall our findings reveal a novel multi-layered feedback circuit depending on Treg cells and regulated by sex hormones to limit VAT inflammation. ATACseq was performed to assess the chromatin accessibility in male and female spleen and VAT resident Tregs to understand sexual dimorphism