Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor
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Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor. / 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.
In: Cells, Vol. 11, No. 16, 2587, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor
AU - Rode, Anna K.O.
AU - Buus, Terkild Brink
AU - Mraz, Veronika
AU - Al-Jaberi, Fatima Abdul Hassan
AU - Lopez, Daniel Villalba
AU - Ford, Shayne L.
AU - Hennen, Stephanie
AU - Eliasen, Ina Primon
AU - Klewe, Ib Vestergaard
AU - Gharehdaghi, Leila
AU - Dragan, Adrian
AU - Rosenkilde, Mette M.
AU - Woetmann, Anders
AU - Skov, Lone
AU - Ødum, Niels
AU - Bonefeld, Charlotte M.
AU - Kongsbak-Wismann, Martin
AU - Geisler, Carsten
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CD4+ T cells
KW - GLP-1R expression
KW - human
U2 - 10.3390/cells11162587
DO - 10.3390/cells11162587
M3 - Journal article
C2 - 36010663
AN - SCOPUS:85136593234
VL - 11
JO - Cells
JF - Cells
SN - 2073-4409
IS - 16
M1 - 2587
ER -
ID: 319161730