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

Anna K.O. Rode, Terkild Brink Buus, Veronika Mraz, Fatima Abdul Hassan Al-Jaberi, Daniel Villalba Lopez, Shayne L. Ford, Stephanie Hennen, Ina Primon Eliasen, Ib Vestergaard Klewe, Leila Gharehdaghi, Adrian Dragan, Mette M. Rosenkilde, Anders Woetmann, Lone Skov, Niels Ødum, Charlotte M. Bonefeld, Martin Kongsbak-Wismann, Carsten Geisler

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Abstract

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.

Original languageEnglish
Article number2587
JournalCells
Volume11
Issue number16
ISSN2073-4409
DOIs
Publication statusPublished - 2022

Keywords

  • CD4+ T cells
  • GLP-1R expression
  • human

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