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

Area of Science:

• Immunology
• Endocrinology
• Metabolism

Background:

• The glucagon-like peptide-1 receptor (GLP-1R) is crucial for metabolism and a therapeutic target for diabetes and obesity.
• Previous research indicated GLP-1R expression in animal T cells, suggesting immune regulatory functions, but its role in human T cells remained unclear.

Purpose of the Study:

• To investigate the expression and function of GLP-1R in human T cells.
• To determine the specific T cell subsets that express GLP-1R and its potential role in immune regulation.

Main Methods:

• Activation of human T cells and analysis of GLP-1R expression.
• Measurement of intracellular cAMP levels upon GLP-1R agonist stimulation.
• Single-cell CITE- and TCR-sequencing of T helper (Th) 1, Th2, Th17, and induced regulatory T (iTreg) cells.
• Detection of GLP-1R+CD4+ T cells in patient skin samples.

Main Results:

• Activated human T cells express functional GLP-1R, confirmed by increased cAMP levels upon agonist stimulation.
• GLP-1R expression was most prominent in induced regulatory T (iTreg) cells (29-34% of FoxP3+CD25+CD127- cells).
• GLP-1R+CD4+ T cells were identified in skin biopsies from patients with allergic contact dermatitis.

Conclusions:

• T cell activation induces functional GLP-1R expression in human CD4+ T cells.
• The high induction of GLP-1R in human iTreg cells suggests a significant role in the anti-inflammatory effects of GLP-1R agonists.
• These findings highlight a novel immunomodulatory function of GLP-1R in humans.