: 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.

Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity / Giovenzana, Anna; Bezzecchi, Eugenia; Bichisecchi, Anita; Cardellini, Sara; Ragogna, Francesca; Pedica, Federica; Invernizzi, Federica; Di Filippo, Luigi; Tomajer, Valentina; Aleotti, Francesca; Scotti, Giulia M; Socci, Carlo; Cesana, Giovanni; Olmi, Stefano; Morelli, Marco J; Falconi, Massimo; Giustina, Andrea; Bonini, Chiara; Piemonti, Lorenzo; Ruggiero, Eliana; Petrelli, Alessandra. - In: ISCIENCE. - ISSN 2589-0042. - 27:3(2024). [10.1016/j.isci.2024.109032]

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

Giovenzana, Anna
Primo
;
Pedica, Federica;Di Filippo, Luigi;Aleotti, Francesca;Olmi, Stefano;Falconi, Massimo;Giustina, Andrea;Bonini, Chiara;Piemonti, Lorenzo;
2024-01-01

Abstract

: 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.
2024
Health sciences
Obesity medicine
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/157516
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