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)-γ 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-γ 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.
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27 November 2006
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November 06 2006
Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
Kojiro Sato,
Kojiro Sato
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
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Ayako Suematsu,
Ayako Suematsu
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
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Kazuo Okamoto,
Kazuo Okamoto
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
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Akira Yamaguchi,
Akira Yamaguchi
2Department of Oral Pathology, Graduate School, and
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Yasuyuki Morishita,
Yasuyuki Morishita
4Department of Human Pathology and
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Yuho Kadono,
Yuho Kadono
5Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
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Sakae Tanaka,
Sakae Tanaka
5Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
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Tatsuhiko Kodama,
Tatsuhiko Kodama
6Department of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
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Shizuo Akira,
Shizuo Akira
7Department of Host Defence, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
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Yoichiro Iwakura,
Yoichiro Iwakura
8Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
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Daniel J. Cua,
Daniel J. Cua
9Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
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Hiroshi Takayanagi
Hiroshi Takayanagi
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
10Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan
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Kojiro Sato
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
Ayako Suematsu
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
Kazuo Okamoto
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
Akira Yamaguchi
2Department of Oral Pathology, Graduate School, and
Yasuyuki Morishita
4Department of Human Pathology and
Yuho Kadono
5Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
Sakae Tanaka
5Department of Orthopaedic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
Tatsuhiko Kodama
6Department of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
Shizuo Akira
7Department of Host Defence, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Yoichiro Iwakura
8Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Daniel J. Cua
9Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
Hiroshi Takayanagi
1Department of Cell Signaling,
3COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
10Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan
CORRESPONDENCE Hiroshi Takayanagi: [email protected]
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-κB ligand; TRAP, tartrate-resistant acid phosphatase; T reg, regulatory T; VitD3, 1,25 (OH)2 vitamin D3.
Received:
August 18 2006
Accepted:
October 12 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (12): 2673–2682.
Article history
Received:
August 18 2006
Accepted:
October 12 2006
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Citation
Kojiro Sato, Ayako Suematsu, Kazuo Okamoto, Akira Yamaguchi, Yasuyuki Morishita, Yuho Kadono, Sakae Tanaka, Tatsuhiko Kodama, Shizuo Akira, Yoichiro Iwakura, Daniel J. Cua, Hiroshi Takayanagi; Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction . J Exp Med 27 November 2006; 203 (12): 2673–2682. doi: https://doi.org/10.1084/jem.20061775
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