[Involvement of αEβ7 (CD103) in the pathogenesis of autoimmune diseases]

αEβ7 (CD103), one of integrin family molecules, is a heterodimer consisting of an αE subunit and a β7 subunit. αEβ7 is expressed in several subsets of lymphocytes including T cells, intestinal intraepithelial lymphocytes and lamina propria lymphocytes. αEβ7 a ligand for E-cadherin, which is mainly expressed in epithelial cells, and an interaction between αEβ7 and E-cadherin results in adhesion of lymphocytes to epithelial cells. We found that EC5 domain, one of domains consisting E-cadherin, was indispensable for binding of E-cadherin with αEβ7. Accumulating evidence suggests that αEβ7 is not only involved in intestinal immune responses but also tissue damages associated with inflammatory diseases including autoimmune diseases. While E-cadherin is constitutively expressed in epithelial cells, the expression of αEβ7 is induced in T cells upon inflammatory stimulation in vitro. In addition, TGF-β1 induces the expression of αEβ7 via a pathway including Smad. These findings raise the possibility that αEβ7 is a potential therapeutic target for inflammatory diseases. We postulate that molecules that interfere with interaction between αEβ7 and E-cadherin are drug candidates for the diseases. We have been focusing on αEβ7 and vigorously investigating the mechanism that underlies the pathogenesis of autoimmune diseases.