α9 Integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis

Masashi Kanayama, Daisuke Kurotaki, Junko Morimoto, Tsuyoshi Asano, Yutaka Matsui, Yosuke Nakayama, Yoshinari Saito, Koyu Ito, Chiemi Kimura, Norimasa Iwasaki, Koji Suzuki, Tanenobu Harada, Hong Mei Li, Jun Uehara, Tadaaki Miyazaki, Akio Minami, Shigeyuki Kon, Toshimitsu Uede

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

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, 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.

Original languageEnglish
Pages (from-to)8015-8025
Number of pages11
JournalJournal of Immunology
Volume182
Issue number12
DOIs
Publication statusPublished - 2009 Jun 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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