Role of the intestinal cytokine microenvironment in shaping the intraepithelial lymphocyte repertoire.

Local resident IELs are composed of distinct subsets of T cells with potent cytolytic and immunoregulatory capacities. As IELs are located within this unique interface between the core of the body and the outside environment, the specific development and function of intestinal IELs must be tightly regulated. To accomplish this, the cytokine microenvironment of the intestine has evolved sophisticated mechanisms that modulate the phenotype, ontogeny, and function of these cells. In this review, we summarize the evidence demonstrating the origin of certain intestinal cytokines, including IL-7, IL-15, IL-2, TGF-β, and SCF and discuss what influence such cytokines may have on IELs. Moreover, we review data suggesting that the abnormal expression of cytokines that leads to the heightened activation of IELs may also contribute to immunopathological responses or exacerbate inflammatory diseases, such as IBD and celiac disease, or promote cancer development and progression. © Society for Leukocyte Biology.