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.
CITATION STYLE
Sumida, H., Lu, E., Chen, H., Yang, Q., Mackie, K., & Cyster, J. G. (2017). GPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility to intestinal damage. Science Immunology, 2(18). https://doi.org/10.1126/sciimmunol.aao1135
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