학술논문
Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor
Document Type
Academic Journal
Author
Rode, Anna K. O.; Buus, Terkild Brink; Mraz, Veronika; Al-Jaberi, Fatima Abdul Hassan; Lopez, Daniel Villalba; Ford, Shayne L.; Hennen, Stephanie; Eliasen, Ina Primon; Klewe, Ib Vestergaard; Gharehdaghi, Leila; Dragan, Adrian; Rosenkilde, Mette M.; Woetmann, Anders; Skov, Lone; Ødum, Niels; Bonefeld, Charlotte M.; Kongsbak-Wismann, Martin; Geisler, Carsten
Source
Cells. August 2022, Vol. 11 Issue 16
Subject
Language
English
ISSN
2073-4409
Abstract
Author(s): Anna K. O. Rode [1,†]; Terkild Brink Buus [1,†]; Veronika Mraz [1]; Fatima Abdul Hassan Al-Jaberi [1]; Daniel Villalba Lopez [1]; Shayne L. Ford [1]; Stephanie Hennen [2]; Ina [...]
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[sup.+] 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[sup.+]CD25[sup.+]CD127[sup.-] iTreg cells. GLP-1R[sup.+] cells showed no difference in their TCR-gene usage nor CDR3 lengths. Finally, we demonstrated the presence of GLP-1R[sup.+]CD4[sup.+] 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[sup.+] T cells. Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R[sup.+] iTreg cells play a key role in the anti-inflammatory effects ascribed to GLP-1R agonists in humans.
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[sup.+] 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[sup.+]CD25[sup.+]CD127[sup.-] iTreg cells. GLP-1R[sup.+] cells showed no difference in their TCR-gene usage nor CDR3 lengths. Finally, we demonstrated the presence of GLP-1R[sup.+]CD4[sup.+] 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[sup.+] T cells. Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R[sup.+] iTreg cells play a key role in the anti-inflammatory effects ascribed to GLP-1R agonists in humans.