title: Alpha9 integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis.
abstract: Osteopontin is critically involved in rheumatoid arthritis; however, the molecular cross-talk between osteopontin and joint cell components that leads to the inflammatory joint destruction is largely unknown. We found that not only osteopontin but also tenascin-C and their common receptor, alpha(9) integrin, are expressed at arthritic joints. The local production of osteopontin and tenascin-C is mainly due to synovial fibroblasts and, to a lesser extent, synovial macrophages. Synovial fibroblasts and macrophages express alpha(9) integrin, and autocrine and paracrine interactions of alpha(9) integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. alpha(9) integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of alpha(9) integrin function with an anti-alpha(9) integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified alpha(9) integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanayama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurotaki
authors.forename: Junko
authors.initials: J
authors.lastname: Morimoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Asano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsui
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Saito
authors.forename: Koyu
authors.initials: K
authors.lastname: Ito
authors.forename: Chiemi
authors.initials: C
authors.lastname: Kimura
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Tanenobu
authors.initials: T
authors.lastname: Harada
authors.forename: Hong Mei
authors.initials: HM
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Uehara
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Akio
authors.initials: A
authors.lastname: Minami
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005347:Fibroblasts; D007167:Immunotherapy; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism*; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000906:Antibodies; D016207:Cytokines; D039001:Integrin alpha Chains; D008024:Ligands; C084613:integrin alpha9