Sato Kojiro, Suematsu Ayako, Okamoto Kazuo, Yamaguchi Akira, Morishita Yasuyuki, Kadono Yuho, Tanaka Sakae, Kodama Tatsuhiko, Akira Shizuo, Iwakura Yoichiro, Cua Daniel J, Takayanagi Hiroshi
Department of Cell Signaling, Graduate School, and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
J Exp Med. 2006 Nov 27;203(12):2673-82. doi: 10.1084/jem.20061775. Epub 2006 Nov 6.
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)-gamma 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-gamma 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.
在传统上被归类为1型辅助性T（Th）细胞疾病的自身免疫性关节炎中，T细胞的激活会导致破骨细胞介导的骨破坏，但是尽管干扰素（IFN）-γ具有抗破骨细胞生成作用，T细胞如何增强破骨细胞生成仍有待阐明。在此，我们研究了各种Th细胞亚群对破骨细胞生成的影响，并确定了Th17（一种特殊的炎症亚群）是连接T细胞激活与骨吸收的破骨细胞生成性Th细胞亚群。白细胞介素（IL）-23-IL-17轴，而非IL-12-IFN-γ轴，不仅对自身免疫性关节炎的发病阶段至关重要，而且对其骨破坏阶段也至关重要。因此，Th17是与T细胞激活相关的骨破坏的一个有力治疗靶点。
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