TY - JOUR
T1 - α9 Integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis
AU - Kanayama, Masashi
AU - Kurotaki, Daisuke
AU - Morimoto, Junko
AU - Asano, Tsuyoshi
AU - Matsui, Yutaka
AU - Nakayama, Yosuke
AU - Saito, Yoshinari
AU - Ito, Koyu
AU - Kimura, Chiemi
AU - Iwasaki, Norimasa
AU - Suzuki, Koji
AU - Harada, Tanenobu
AU - Li, Hong Mei
AU - Uehara, Jun
AU - Miyazaki, Tadaaki
AU - Minami, Akio
AU - Kon, Shigeyuki
AU - Uede, Toshimitsu
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/6/15
Y1 - 2009/6/15
N2 - 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, α9 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 α9 integrin, and autocrine and paracrine interactions of α9 integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. α9 integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of α9 integrin function with an anti-α9 integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified α9 integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.
AB - 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, α9 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 α9 integrin, and autocrine and paracrine interactions of α9 integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. α9 integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of α9 integrin function with an anti-α9 integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified α9 integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.
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U2 - 10.4049/jimmunol.0900725
DO - 10.4049/jimmunol.0900725
M3 - Article
C2 - 19494327
AN - SCOPUS:67649204689
VL - 182
SP - 8015
EP - 8025
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -