Innate PD-L1 limits T cell-mediated adipose tissue inflammation and ameliorates diet-induced obesity

Schwartz C, Schmidt V, Deinzer A, Hawerkamp HC, Hams E, Bayerlein J, Roeger O, Bailer M, Krautz C, Elgendy A, Elshafei M, Heneghan HM, Hogan AE, O'Shea D, Fallon PG (2022)

Publication Type: Journal article, Original article

Publication year: 2022

Journal

Science Translational Medicine American Association for the Advancement of Science

Book Volume: 14

Pages Range: eabj6879-

Journal Issue: 635

DOI: 10.1126/scitranslmed.abj6879

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.

Authors with CRIS profile

Christian Schwartz Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Viviane Schmidt Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Jasmin Bayerlein Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Christian Krautz Department of Surgery Amr Elgendy Department of Surgery Moustafa Elshafei Department of Surgery

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

J079: Functional impact of PD-L1:PD-1-interactions on diet-induced obesity and dysbiosis Sept. 1, 2019 - Aug. 31, 2022

Involved external institutions

Trinity College Dublin IE Ireland (IE) University College Dublin (UCD) IE Ireland (IE) St Vincent's University Hospital IE Ireland (IE)

How to cite

APA:

Schwartz, C., Schmidt, V., Deinzer, A., Hawerkamp, H.C., Hams, E., Bayerlein, J.,... Fallon, P.G. (2022). Innate PD-L1 limits T cell-mediated adipose tissue inflammation and ameliorates diet-induced obesity. Science Translational Medicine, 14(635), eabj6879-. https://doi.org/10.1126/scitranslmed.abj6879

MLA:

Schwartz, Christian, et al. "Innate PD-L1 limits T cell-mediated adipose tissue inflammation and ameliorates diet-induced obesity." Science Translational Medicine 14.635 (2022): eabj6879-.

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