Amplifying elements of arthritis and joint destruction

Ann Rheum Dis. 2007 Nov;66 Suppl 3(Suppl 3):iii45-8. doi: 10.1136/ard.2007.079830.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and variable degrees of bone and cartilage erosion. Studies in animal models of arthritis provide insight into elements which can amplify destructive features. The presence of immune complexes in the joint makes arthritis more erosive. Although considerable bone erosion still occurs in the absence of FcgammaR triggering by immune complexes, through cytokine-induced RANKL and direct osteoclast activation, cartilage erosion is heavily dependent on the FcgammaR pathway. T cell factors such as IFNgamma and IL17 further amplify erosion through upregulation of the damaging FcgammaRI and stimulation of the influx of granulocytes, respectively. Apart from immune elements, environmental pressure and components of tissue damage contribute through innate pathways. Spontaneous T cell-dependent arthritis in IL1Ra-/- mice is absent under germ-free conditions, and markedly suppressed in TLR4-deficient mice. Moreover, TLR4 blocking with a receptor antagonist suppresses erosive arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Antibody Complex / immunology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Bone Resorption / immunology
  • Cartilage, Articular / immunology
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Joints / immunology*
  • Joints / pathology
  • Mice
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 4 / immunology

Substances

  • Antigen-Antibody Complex
  • Interleukin-17
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Interferon-gamma