alpha(9) Integrin and Its Ligands Constitute Critical Joint Microenvironments for Development of Autoimmune Arthritis

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

来源：The Journal of Immunology, 2009, 182(12): 8015-8025.

DOI：10.4049/jimmunol.0900725

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 anti 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. The Journal of Immunology, 2009, 182: 8015-8025.

• 出版日期2009-6-15
• 单位河北医科大学