title: β7 Integrin controls mast cell recruitment, whereas αE integrin modulates the number and function of CD8+ T cells in immune complex-mediated tissue injury.
abstract: 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 αE and β7 integrin in IC-mediated tissue injury, peritoneal and cutaneous reverse-passive Arthus reaction was examined in mice lacking αE integrin (αE(-/-)) or β7 integrin (β7(-/-)). Both αE(-/-) and β7(-/-) mice exhibited significantly attenuated neutrophil infiltration in the peritoneal and cutaneous Arthus reaction. β7 integrin deficiency, not αE integrin deficiency, significantly reduced the number of mast cells in the peritoneal cavity, which was consistent with the result that mast cells expressed only α4β7 integrin, not αEβ7 integrin. αE(-/-) mice instead revealed the reduction of CD8(+) T cells in the peritoneal cavity, and nearly half of them in wild-type mice expressed αE integrin. These αE(+)CD8(+) T cells produced more proinflammatory cytokines than αE(-)CD8(+) T cells, and adoptive transfer of αE(+)CD8(+) T cell into αE(-/-) recipients restored cutaneous and peritoneal Arthus reaction. These results suggest that in the peritoneal and cutaneous reverse-passive Arthus reaction, α4β7 integrin is involved in the migration of mast cells for initial IC recognition. αEβ7 integrin, in contrast, contributes by recruiting αE(+)CD8(+) T cells, which produce more proinflammatory cytokines than αE(-)CD8(+) T cells and amplify IC-mediated inflammation.
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Yuri
authors.initials: Y
authors.lastname: Masui
authors.forename: Koichi
authors.initials: K
authors.lastname: Yanaba
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007105:Immune Complex Diseases / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000276:immunology*; D039641:Integrin beta Chains / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; C091367:alpha E integrins; C091368:integrin beta7