Integrin alpha(E)(CD103)beta(7) mediates adhesion to intestinal microvascular endothelial cell lines via an E-cadherin-independent interaction

Integrins are important for T cell interactions with endothelial cells, Bec ause the integrin alpha (E)beta (7) is expressed on some circulating gut-ho ming T cells and as T cell numbers are reduced in the intestinal lamina pro pria of alpha (E)-deficient mice, we evaluated whether alpha (E)beta (7) me diates binding to intestinal endothelial cells. We found that anti-alpha (E )beta (7) mAbs partially blocked the binding of cultured intraepithelial T cells to human intestinal microvascular endothelial cells (HIMEC), Furtherm ore, alpha (E)beta (7)-transfected K562 cells bound more efficiently than v ector-transfected K562 cells to HIMEC. Finally, HIMEC bound directly to an alpha (E)beta (7)-Fc fusion protein. These interactions were partially bloc ked by anti-alpha (E)beta (7) mAbs, and endothelial cell binding to the alp ha (E)beta (7)-Fc was dependent upon the metal ion-dependent adhesion site within the alpha (E) A domain. Of note, the HIMEC lacked expression of E-ca dherin, the only known alpha (E)beta (7) counterreceptor as assessed by fun ctional studies, flow cytometry, and RT-PCR, Thus, HIMEC/alpha (E)beta (7) binding was independent of E-cadherin. In addition, this interaction appear ed to be tissue selective, as HIMEC bound to the alpha (E)beta (7)-Fc, wher eas microvascular endothelial cells from the skin did not. Finally, there w as evidence for an alpha (E)beta (7) ligand on intestinal endothelial cells in vivo, as alpha (E)beta (7) expression enhanced lymphocyte binding aroun d vessels in the lamina propria in tissue sections. Thus, we have defined a novel interaction for alpha (E)beta (7) at a nonepithelial location. These studies suggest a role for alpha (E)beta (7) in interactions with the inte stinal endothelium that may have implications for intestinal T cell homing or functional responses.