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Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity

ABSTRACT: Obesity is characterized by accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys). These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRβ repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest that dysglycemia in individuals with obesity is associated with recirculation of a heterogeneous population of partially dysfunctional PD-1+CD4 Tconv cells. These changes may contribute to the inter-organ crosstalk underlying IR

ORGANISM(S): Homo sapiens

PROVIDER: GSE237338 | GEO | 2024/02/09

REPOSITORIES: GEO

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