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

Autor:	Schwartz C; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany.; Medical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, D-91054 Erlangen, Germany.; Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, D02R590 Dublin 2, Ireland., Schmidt V; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Deinzer A; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Hawerkamp HC; Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, D02R590 Dublin 2, Ireland., Hams E; Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, D02R590 Dublin 2, Ireland., Bayerlein J; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Röger O; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Bailer M; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Krautz C; Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., El Gendy A; Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Elshafei M; Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, D-91054 Erlangen, Germany., Heneghan HM; Department of Surgery, St. Vincent's University Hospital and University College Dublin, D04T6F4 Dublin 4, Ireland., Hogan AE; Kathleen Lonsdale Human Health Institute, Maynooth University, W23F2H6 Maynooth, Co. Kildare, Ireland.; Obesity Immunology Research, St. Vincent's University Hospital and University College Dublin, D04T6F4 Dublin 4, Ireland., O'Shea D; Obesity Immunology Research, St. Vincent's University Hospital and University College Dublin, D04T6F4 Dublin 4, Ireland., Fallon PG; Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, D02R590 Dublin 2, Ireland.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2022 Mar 09; Vol. 14 (635), pp. eabj6879. Date of Electronic Publication: 2022 Mar 09.
DOI:	10.1126/scitranslmed.abj6879
Abstrakt:	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.
Databáze:	MEDLINE
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