期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 14, 期 635, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.abj6879
关键词
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资金
- National Children's Research Centre and Science Foundation Ireland [10/IN.1/B3004]
- Irish Research Council Government of Ireland [GOIPD/2019/193]
- Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg [J79]
- Else Kroner-Fresenius-Stiftung [2019_A181]
Obesity is a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis. A recent study found that the costimulatory molecule programmed death-ligand 1 (PD-L1) plays a role in limiting diet-induced obesity. PD-L1 expression on dendritic cells (DCs) is essential for obesity control.
Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy.
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