Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

作者：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 · 发表于：The Journal of Experimental Medicine · 年份：2006 · DOI：10.1084/jem.20061775 · 被引用次数：1559 · 研究领域：Bone Metabolism and Diseases、NF-κB Signaling Pathways、Cytokine Signaling Pathways and Interactions

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.