Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction.
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.
Sato
Kojiro
K
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.
Suematsu
Ayako
A
Okamoto
Kazuo
K
Yamaguchi
Akira
A
Morishita
Yasuyuki
Y
Kadono
Yuho
Y
Tanaka
Sakae
S
Kodama
Tatsuhiko
T
Akira
Shizuo
S
Iwakura
Yoichiro
Y
Cua
Daniel J
DJ
Takayanagi
Hiroshi
H
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D001862:Bone Resorption / Q000276:immunology* / Q000473:pathology; D001842:Bone and Bones / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology