β7 Integrin Controls Mast Cell Recruitment, whereas αE Integrin Modulates the Number and Function of CD8+ T Cells in Immune Complex-Mediated Tissue Injury

Immune complex (IC) deposition causes significant tissue injury associated with various autoimmune diseases such as vasculitis. In the cascade of inflammation, cell-to-cell and cell-to-matrix adhesion via adhesion molecules are essential. To assess the role of alpha E and beta 7 integrin in IC-mediated tissue injury, peritoneal and cutaneous reverse-passive Arthus reaction was examined in mice lacking alpha E integrin (alpha E-/-) or beta 7 integrin (beta 7(-/-)). Both alpha E-/-and b beta 7(-/)-mice exhibited significantly attenuated neutrophil infiltration in the peritoneal and cutaneous Arthus reaction. b7 integrin deficiency, not aE integrin deficiency, significantly reduced the number of mast cells in the peritoneal cavity, which was consistent with the result that mast cells expressed only alpha 4 beta 7 integrin, not alpha E beta 7 integrin. alpha E-/-mice instead revealed the reduction of CD8(+) T cells in the peritoneal cavity, and nearly half of them in wild-type mice expressed aE integrin. These alpha E(+)CD8(+) T cells produced more proinflammatory cytokines than alpha E(-)CD8(+) T cells, and adoptive transfer of alpha E(+)CD8(+) T cell into alpha E-/-recipients restored cutaneous and peritoneal Arthus reaction. These results suggest that in the peritoneal and cutaneous reverse-passive Arthus reaction, a4b7 integrin is involved in the migration of mast cells for initial IC recognition. alpha E beta 7 integrin, in contrast, contributes by recruiting alpha E(+)CD8(+) T cells, which produce more proinflammatory cytokines than alpha E(-)CD8(+) T cells and amplify IC-mediated inflammation. The Journal of Immunology, 2014, 192: 4112-4121.