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

Summary

Obesity is characterized by the 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), without a concomitant increase in apoptosis. 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 a potential role for partially dysfunctional PD-1 ⁺CD4 Tconv cells as inter-organ mediators of IR in obese patients with dysglycemic.

Graphical abstract

Highlights

• •

  Dysglycemic obesity associates with reduced partially dysfunctional PD-1+CD4 Tconv in VAT

• •

  Dysglycemia induces alterations in the TCRβ repertoire of CD4 Tconv cells in obese VAT

• •

  Dysglycemia prompts an increased recirculation of PD-1+CD4 Tconv cells to the bloodstream

• •

  PD-1+CD4 Tconv cells accumulate in the liver of patients with dysglycemic

Abstract

Health sciences; Obesity medicine