Recent advances in roles of G-protein coupled receptors in intestinal intraepithelial lymphocytes

Abstract

Intestinal intraepithelial lymphocytes (IELs) potentially provide the first line of immune defense against enteric pathogens. In addition, there is growing evidence supporting the involvement of IELs in the pathogenesis of gut disorders such as inflammatory bowel diseases. Various kinds of molecules are involved in the dynamics of IELs, such as homing to the intestinal epithelium and retention in the intestinal mucosa. G protein-coupled receptors (GPCRs) comprise the largest family of cell surface receptors and regulate many biological responses. Although some GPCRs, like CCR9, have been implicated to have roles in IEL homing, little is still known regarding the functional roles of GPCRs in IEL biology. In this review, we provide a concise overview of recent advances in the roles of novel GPCRs like GPR55 and GPR18 in the dynamics of IELs.

Keywords: G-protein coupled receptors; dynamics; gut immunology; intestinal intraepithelial lymphocytes.

Fig. 1.

Dynamics of intestinal intraepithelial lymphocytes (IELs) regulated by G-protein coupled receptors (GPCRs) in the small intestine. A variety of GPCRs are involved in the IEL homing to the intestinal epithelium. CCR9 and GPR18 have roles in augmenting the accumulation of CD8 T cells in the intestinal intraepithelial lymphocyte compartment. On the other hand, GPR55, a receptor that mediates migration inhibition in response to lysophosphatidylinositol (LPI), negatively regulates CD8αα⁺TCRγδ⁺ IEL accumulation in the epithelium. GPR18 L, ligands for GPR18.