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¹ Department of Cell Signaling, ² Department of Oral Pathology, Graduate School, and ³ COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
⁴ Department of Human Pathology and ⁵ Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
⁶ Department of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
⁷ Department of Host Defence, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
⁸ Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
⁹ Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
¹⁰ Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan

CORRESPONDENCE Hiroshi Takayanagi: taka.csi{at}tmd.ac.jp

In autoimmune arthritis, traditionally classified as a T helper (Th) type 1 disease, the activation of T cells results in bone destruction mediated by osteoclasts, but how T cells enhance osteoclastogenesis despite the anti-osteoclastogenic effect of interferon (IFN)- remains to be elucidated. Here, we examine the effect of various Th cell subsets on osteoclastogenesis and identify Th17, a specialized inflammatory subset, as an osteoclastogenic Th cell subset that links T cell activation and bone resorption. The interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN- axis, is critical not only for the onset phase, but also for the bone destruction phase of autoimmune arthritis. Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation.

Abbreviations used: BMC, BM cell; BMM, BM-derived monocyte/macrophage precursor cell; M-CSF, macrophage colony-stimulating factor; MNC; multinucleated cell; PGE₂, prostaglandin E₂; RA, rheumatoid arthritis; RANKL, receptor activator of NF-B ligand; TRAP, tartrate-resistant acid phosphatase; T reg, regulatory T; VitD₃, 1,25 (OH)₂ vitamin D₃.

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