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

• DOI: 10.1016/j.isci.2024.109032
• Publication Date: 2024-02-01T18:08:49Z
• Authors: Anna Giovenzana; Eugenia Bezzecchi; Anita Bichisecchi; Sara Cardellini; Francesca Ragogna; Federica Pedica; Federica Invernizzi; Luigi Di Filippo; Valentina Tomajer; Francesca Aleotti; Giulia M. Scotti; Carlo Socci; Giovanni Cesana; Stefano Olmi; Marco J. Morelli; Massimo Falconi; Andrea Giustina; Chiara Bonini; Lorenzo Piemonti; Eliana Ruggiero; Alessandra Petrelli
• Keywords: Obesity medicine; Health sciences; Obesity medicine;; Science; Q; Health sciences; Article

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.