Functional characterization of glucagon-like peptide 1 receptor in CD8 alpha alpha murine small intestinal intraepithelial lymphocytes

• Main Authors: Yen-Wen Huang, 黃彥文
• Other Authors: Nan-Shih Liao
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/15377229603222049566

碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 100 === Glucagon-like peptide 1 (GLP-1) is an incretin hormone secreted from intestinal endocrine L-cells in response to food intake. The functions of GLP-1 in several tissues have been demonstrated including stimulation of insulin secretion, decrease of appetite, neuroprotection and cardioprotection. GLP-1 exerts its action through activation of GLP-1 receptor (GLP-1R). Recent studies reported the expression of GLP-1R by certain T cell populations and by macrophages. However, the function of GLP-1R in these cells or in the immune system remains elusive. Intestinal intraepithelial lymphocytes (iIEL) are unique T cells residing in the intestinal epithelium. More than half of iIELs in the murine small intestine are CD8aa+. Here I found that CD8aa+ iIELs express GLP-1R mRNA and produce cAMP upon stimulation with a GLP-1R agonist, exendin-4. The cAMP production was blocked by a GLP-1R antagonist, exnendin (9-39). Using transcriptome analysis and qRT-PCR validation, I found that GLP-1R activation induced the expression of Pdcd1 while suppressed the expression of chemokine genes, including Ccl1, Ccl3, Ccl4 and Xcl1. The production of CCL3 and CCL4 proteins was also diminished by GLP-1R stimulation. Moreover, I found that TCR-induced IFN-g production was inhibited by GLP-1R activation in CD8aa+ iIELs. The level of phosphorylated ERK1/2 induced by TCR stimulation also decreased in response to GLP-1R activation. These results suggest that GLP-1R has the anti-inflammatory and immunoregulatory functions in CD8aa+ iIELs. Taken together, I uncover a previously unknown function of GLP-1R in CD8aa+ iIELs.