Rapid adipose tissue expansion triggers proliferation of memory adipose tissue T cells and accumulation of novel T helper 2 (Th2) regulatory cells 3894

Abstract Description Obesity generates a pro-inflammatory state contributing to immune dysregulation and metabolic disease. Adipose tissue is a site of obesity-induced inflammation. Adipose tissue T cells (ATTs) from obese mice and humans with obesity have an exhausted phenotype. We sought to determine the factors that regulate ATT function using short-term HFD (stHFD). We hypothesized that ATTs respond to early fat expansion and these responses contribute to the orchestration of adipose tissue inflammation with obesity. We placed mice on stHFD (up to 14 days) and assessed ATT kinetics. Mice on HFD gained significantly more total body, epidydimal white adipose tissue (eWAT), and inguinal WAT (iWAT) weight compared to controls. We observed significant proliferation of memory, but not naïve, ATTs with 7 days of HFD in all fat depots assessed. Further, we performed Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) on FACS sorted eWAT ATTs from mice fed a HFD for 0 or 14 days. We identified a striking decrease in regulatory T cells (Tregs) and γδ T cells, with an increase in novel “T helper 2 (Th2) regulatory” cells with 14 days of HFD. Th2 regulatory cells express hallmark Th2 genes but also increase expression of immune regulatory genes such as Ctla2a, Furin, and Areg with HFD. These data suggest dynamic changes occur within ATT subpopulations with stHFD that potentiate obesity-associated adipose tissue inflammation. Funding Sources Supported by P30DK089503, K99DK136934, and R01DK090262. Topic Categories Mucosal and Regional Immunology (MUC)