Epithelial and γδ T cell CD47 have complementary yet distinct roles in regulating γδ intraepithelial lymphocyte migration

Intraepithelial lymphocytes expressing the {gamma}{delta} T cell receptor ({gamma}{delta} IEL) continuously survey the intestinal epithelium to promote mucosal host defense. Although {gamma}{delta} IELs migrate in and out of the lateral intercellular space (LIS) between adjacent enterocytes, the molecular mechanisms governing their migratory behavior are incompletely understood. Based on the known role of CD47, or integrin associated protein (IAP), in mediating neutrophil transepithelial migration, we investigated whether CD47 expression reflects a conserved mechanism regulating {gamma}{delta} IEL surveillance behavior. Here, we report that conditional CD47 deletion on intestinal epithelial cells or {gamma}{delta} T cells had no effect on IEL composition. Using intravital imaging, we identified complementary roles for CD47 on {gamma}{delta} IELs and epithelial cells, with epithelial CD47 restricting {gamma}{delta} IEL motility and {gamma}{delta} T-cell-derived CD47 promoting cell migration. Further investigation revealed that both CD47 and CD18 contribute to {gamma}{delta} IEL surveillance behavior, although CD47 regulates {gamma}{delta} IEL migration in a CD18-independent manner.