Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction

Cells

Brigitte Le Magueresse-Battistoni¹  Assia Eljaafari¹  Maud Robert¹  Julien Pestel¹  Julia Watson¹  Hubert Vidal¹  Stephanie Chanon¹  Emmanuel Disse¹ 

[1] Inserm U1060, University Claude Bernard Lyon 1, INRAE U1397, 69310 Pierre Bénite, France;

关键词: PD-1/PD-L1 immune checkpoints;    T cell dysfunction;    adipose-tissue-derived mesenchymal stem cells;    white adipose tissue;    inflammation;    obesity;   

DOI  :  10.3390/cells10102645

来源: DOAJ

【 摘 要 】

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.

【 授权许可】

Unknown