Dec 13, 2018

TDAG8 (GPR65) Inhibits Intestinal Inflammation in the DSS-Induced Experimental Colitis Mouse Model

BioRxiv : the Preprint Server for Biology
Edward J SanderlinLi V Yang


T cell death-associated gene 8 (TDAG8, also known as GPR65) is a proton-sensing G protein-coupled receptor (GPCR) predominantly expressed in immune cells. Genome-wide association studies identify TDAG8 as a susceptibility candidate gene linked to several human inflammatory diseases including inflammatory bowel disease (IBD), asthma, spondyloarthritis, and multiple sclerosis. In this study, our results demonstrate that mice deficient of TDAG8 exhibited more severe inflammatory phenotypes than wild-type mice in a chronic dextran sulfate sodium (DSS)-induced colitis mouse model. Several disease parameters, such as diarrhea, colon shortening, fibrosis, histopathological score, and mesenteric lymph node enlargement were aggravated in TDAG8-null mice in comparison to wild-type mice treated with DSS. Increased leukocyte infiltration and myofibroblast expansion were observed in colonic tissues of DSS-treated TDAG8-null mice. These changes may represent a cellular basis of the observed exacerbation of intestinal inflammation and fibrosis in these mice. In line with high expression of TDAG8 in infiltrated leukocytes, real-time RT-PCR revealed that TDAG8 mRNA expression was increased in inflamed intestinal tissue samples of IBD patients w...Continue Reading

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Mentioned in this Paper

Real-Time Polymerase Chain Reaction
Genome-Wide Association Study
Inflammatory Myofibroblastic Tumor
Immune Effector Cell
G-Protein-Coupled Receptors
Cessation of Life

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