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

J Exp Med. 2006 Nov 27;203(12):2673-82. doi: 10.1084/jem.20061775. Epub 2006 Nov 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Bone Resorption / immunology*
  • Bone Resorption / pathology
  • Bone and Bones / immunology*
  • Bone and Bones / pathology*
  • Cell Differentiation / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoclasts / immunology*
  • Osteoclasts / pathology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology