Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells

Abstract

Aims/hypothesis Glucagon-like peptide-1 receptor (GLP-1R) agonists improve glucose control in animals and humans with type 1 diabetes. However, there is little information on the role of the GLP-1R in the immune system. We studied the role of the GLP-1R in immune function in wild-type (WT) and nonobese diabetic (NOD) and Glp1r

GLP-1R Agonists Modulate Enteric Immune Responses Through the Intestinal Intraepithelial Lymphocyte GLP-1R

“…Given the lack of specificity of the majority of commercially available GLP-1R antibodies and existing discrepancies in studies reporting sites of intestinal GLP-1R expression, we initiated studies to localize the sites of endogenous GLP-1R mRNA expression in the murine gut. Although mRNA transcripts encoding a functional GLP-1R were detected in rodent immune cells isolated from spleen, lymph nodes, and bone marrow (19), the current experiments reveal that IEL Glp1r expression is considerably more abundant relative to Glp1r mRNA levels in other mouse lymphoid organs. Several lines of evidence support the functional importance of the newly described IEL GLP-1R.…”

“…cDNA synthesis and assessment of full-length Glp1r mRNA expression were performed as described (16,19). Real-time qPCR was performed on an ABI PRISM 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA) with TaqMan Universal PCR Master Mix and TaqMan Gene Expression Assays (Applied Biosystems).…”

Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity and psoriasis: diabetes meets dermatology

“…1), GLP-1Rs have subsequently been localised to the central and peripheral nervous system, lung, kidney, gastrointestinal tract, heart and blood vessels [3], where they mediate a diverse number of actions distinct from control of glucose homeostasis [4]. More recent studies have demonstrated widespread Glp1r expression in numerous immune cell subpopulations, including thymoyctes, splenocytes, bone marrow-derived cells, and regulatory T cells [5]. Consistent with the results reported by Hogan et al, GLP-1R agonists have previously been shown to increase cAMP formation in multiple lymphocyte populations in a GLP-1R-and exendin (9-39)-dependent manner [5].…”

“…More recent studies have demonstrated widespread Glp1r expression in numerous immune cell subpopulations, including thymoyctes, splenocytes, bone marrow-derived cells, and regulatory T cells [5]. Consistent with the results reported by Hogan et al, GLP-1R agonists have previously been shown to increase cAMP formation in multiple lymphocyte populations in a GLP-1R-and exendin (9-39)-dependent manner [5]. Furthermore, several reports have described disease remission and enhanced numbers of regulatory T cells in experimental murine models of autoimmune type 1 diabetes treated with GLP-1R agonists in the absence of concomitant therapy with immunomodulatory agents [6,7].…”

“…Furthermore, several reports have described disease remission and enhanced numbers of regulatory T cells in experimental murine models of autoimmune type 1 diabetes treated with GLP-1R agonists in the absence of concomitant therapy with immunomodulatory agents [6,7]. GLP-1R activation also modestly reduced stromal cell-derived factor-1-enhanced lymphocyte migration in human CD4 + lymphocytes [8], whereas genetic disruption of Glp1r produced detectable defects in thymocyte and lymphocyte proliferation following stimulation ex vivo [5]. Hence, the available evidence supports a role for the GLP-1R in controlling lymphocyte proliferation and/or migration in murine and human immune cells.…”