α4β7 integrin is essential for contact hypersensitivity by regulating migration of T cells to inflammatory skin. (44.11)

Abstract

β7 integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, MAdCAM-1, which is preferentially expressed in gut-associated lymphoid tissues. Although the importance of α4β7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated. Here we show that β7 integrin-deficient mice, not αE integrin-deficient mice, are defective in contact hypersensitivity (CHS) responses. β7 integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from β7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized β7 integrin-deficient T cells are able to respond to antigen stimuli in vitro, and elicit CHS responses when directly injected into the skin. However, they are defective in reaching the skin under inflammatory conditions, resulting in reduced CHS responses when intravenously injected. Furthermore, T cells treated with anti-α4β7 integrin neutralizing antibody elicit impaired CHS responses. These results indicate a novel role of α4β7 integrin in regulating T cell migration to inflammatory skin.