Schwartz, Christian and Schmidt, Viviane and Deinzer, Andrea and Hawerkamp, Heike C. and Hams, Emily and Bayerlein, Jasmin and Röger, Ole and Bailer, Moritz and Krautz, Christian and El Gendy, Amr and Elshafei, Moustafa and Heneghan, Helen M. and Hogan, Andrew E. and O’Shea, Donal and Fallon, Padraic G. (2022) Innate PD-L1 limits T cell–mediated adipose tissue inflammation and ameliorates diet-induced obesity. Science Translational Medicine, 14 (635). ISSN 1946-6234

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Abstract

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.

Item Type:	Article
Keywords:	Innate; PD-L1 limits; T cell–mediated; adipose tissue; inflammation; ameliorates; diet-induced obesity;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17900
Identification Number:	https://doi.org/10.1126/scitranslmed.abj6879
Depositing User:	Andrew Hogan
Date Deposited:	29 Nov 2023 16:19
Journal or Publication Title:	Science Translational Medicine
Publisher:	American Association for the Advancement of Science
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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