RESEARCH - Alpha9 integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis

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J Immunol. 2009 Jun 15;182(12):8015-25.

Alpha9 integrin and its ligands constitute critical joint

microenvironments for development of autoimmune arthritis.

Kanayama M, Kurotaki D, Morimoto J, Asano T, Matsui Y, Nakayama Y,

Saito Y, Ito K, Kimura C, Iwasaki N, Suzuki K, Harada T, Li HM, Uehara

J, Miyazaki T, Minami A, Kon S, Uede T.

Division of Molecular Immunology, Institute for Genetic Medicine,

Hokkaido University, Sapporo, Japan.

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.

PMID: 19494327

http://www.ncbi.nlm.nih.gov/pubmed/19494327

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