期刊
CELLS
卷 10, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/cells10102645
关键词
T cell dysfunction; adipose-tissue-derived mesenchymal stem cells; white adipose tissue; inflammation; obesity; IFN gamma; PD-1/PD-L1 immune checkpoints
类别
资金
- IDEX Lyon [IDEX/COV/2020-12]
The study revealed that PD-L1 is overexpressed in the adipose tissue of obese individuals, leading to T cell dysfunction and notably reduced cytolytic activity. PD-L1 plays a role in T cell dysfunction mediated by obese ASC.
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 IFN gamma. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFN gamma 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.
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