Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor.

Autor:	Rode AKO; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Buus TB; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Mraz V; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Al-Jaberi FAH; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Lopez DV; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Ford SL; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Hennen S; Grünenthal GmbH, Zieglerstr. 6, 52078 Aachen, Germany., Eliasen IP; Novo Nordisk A/S, DK-2760 Måløv, Denmark., Klewe IV; Lundbeck, DK-2500 Copenhagen, Denmark., Gharehdaghi L; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Dragan A; Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Rosenkilde MM; Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Woetmann A; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Skov L; Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, DK-2900 Copenhagen, Denmark., Ødum N; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Bonefeld CM; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Kongsbak-Wismann M; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark., Geisler C; The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Cells [Cells] 2022 Aug 19; Vol. 11 (16). Date of Electronic Publication: 2022 Aug 19.
DOI:	10.3390/cells11162587
Abstrakt:	The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an important therapeutic target in diabetes and obesity. Recent studies in experimental animals have shown that certain subsets of T cells express functional GLP-1R, indicating an immune regulatory role of GLP-1. In contrast, less is known about the expression and function of the GLP-1R in human T cells. Here, we provide evidence that activated human T cells express GLP-1R. The expressed GLP-1R was functional, as stimulation with a GLP-1R agonist triggered an increase in intracellular cAMP, which was abrogated by a GLP-1R antagonist. Analysis of CD4 + T cells activated under T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cell differentiation conditions indicated that GLP-1R expression was most pronounced in induced Treg (iTreg) cells. Through multimodal single-cell CITE- and TCR-sequencing, we detected GLP-1R expression in 29-34% of the FoxP3 + CD25 + CD127 - iTreg cells. GLP-1R + cells showed no difference in their TCR-gene usage nor CDR3 lengths. Finally, we demonstrated the presence of GLP-1R + CD4 + T cells in skin from patients with allergic contact dermatitis. Taken together, the present data demonstrate that T cell activation triggers the expression of functional GLP-1R in human CD4 + T cells. Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R + iTreg cells play a key role in the anti-inflammatory effects ascribed to GLP-1R agonists in humans.
Databáze:	MEDLINE
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