脂肪组织
炎症
免疫系统
先天性淋巴细胞
T细胞
免疫学
平衡
生物
脂肪组织巨噬细胞
先天免疫系统
内分泌学
内科学
细胞生物学
医学
白色脂肪组织
作者
Charles E. Schwartz,Viviane Bom Schmidt,Andrea Deinzer,Heike C Hawerkamp,Emily Hams,Jasmin Bayerlein,Ole Röger,Moritz Bailer,Christian Krautz,Amr El Gendy,Moustafa Elshafei,Helen M. Heneghan,Andrew E. Hogan,Donald C. O'Shea,Padraic G. Fallon
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2022-03-09
卷期号:14 (635)
被引量:12
标识
DOI:10.1126/scitranslmed.abj6879
摘要
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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