biostudies-literatureUnknown2(18)Sumida HNIDA NIH HHSHoward Hughes Medical InstituteNIAID NIH HHSIntraepithelial lymphocytes (IELs) of the small intestine are intimately associated with the epithelial cells. Yet, the factors controlling their migration and interaction dynamics are poorly understood. We demonstrate that GPR55, a receptor that mediates migration inhibition in response to lysophosphatidylinositol (LPI), negatively regulates T cell receptor ?? (TCR??) IEL accumulation in the small intestine. Intravital imaging studies show that GPR55-deficient IELs migrate faster and interact more extensively with epithelial cells. GPR55 also negatively regulates T cell homing to the small intestine and ??T cell egress from Peyer's patches. GPR55 deficiency or short-term antagonist treatment protects from nonsteroidal anti-inflammatory drug-induced increases in intestinal permeability. These findings identify a migration-inhibitory receptor that restrains IEL-epithelial cell cross-talk and show that antagonism of this receptor can protect from intestinal barrier dysfunction.Science immunologyhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC5847323biostudies-literatureGPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility to intestinal damage.PMC5847323K05 DA021696R01 AI045073T32 AI007334R01 AI040098Cyster JGSumida HMackie KLu EChen HYang QfalseGPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility to intestinal damage.Intraepithelial lymphocytes (IELs) of the small intestine are intimately associated with the epithelial cells. Yet, the factors controlling their migration and interaction dynamics are poorly understood. We demonstrate that GPR55, a receptor that mediates migration inhibition in response to lysophosphatidylinositol (LPI), negatively regulates T cell receptor ?? (TCR??) IEL accumulation in the small intestine. Intravital imaging studies show that GPR55-deficient IELs migrate faster and interact more extensively with epithelial cells. GPR55 also negatively regulates T cell homing to the small intestine and ??T cell egress from Peyer's patches. GPR55 deficiency or short-term antagonist treatment protects from nonsteroidal anti-inflammatory drug-induced increases in intestinal permeability. These findings identify a migration-inhibitory receptor that restrains IEL-epithelial cell cross-talk and show that antagonism of this receptor can protect from intestinal barrier dysfunction.2017-01-01T00:00:00Z2017 Dec2020-10-29T14:13:55Z2019-03-26T23:40:20ZS-EPMC58473232922209010.1126/sciimmunol.aao1135