Nature Reviews Rheumatology 5, 667-676 (December 2009) | doi:10.1038/nrrheum.2009.217

There is a Correction (1 January 2010) associated with this article.

Subject Category: Immunology

Osteoimmunology and the effects of the immune system on bone

Hiroshi Takayanagi  About the author


In the pathogenesis of bone destruction associated with rheumatoid arthritis, the synovium is a site of active interplay between immune and bone cells. The interaction between T cells and osteoclasts is a critical issue in the field of osteoimmunology. Accumulating evidence lends support to the theory that interleukin-17-producing T-helper cells induce the expression of receptor activator of nuclear factor kappaB ligand in synovial cells, which, together with inflammatory cytokines, stimulates the differentiation and activation of bone-resorbing osteoclasts. In addition to cellular interactions via cytokines, the immune and skeletal systems share various other molecules, including transcription factors, signaling molecules and membrane receptors. Studies of intracellular signaling mechanisms in osteoclasts have revealed that numerous immunomodulatory molecules are involved in the regulation of bone metabolism. The regulation of immune cells by bone cells is a new feature of the investigative area of osteoimmunology that implies the novel concept of the bone marrow being a crucial part of the immune system. The emerging field of osteoimmunology is important for increasing our understanding of how antirheumatic drugs (including anti-cytokine biologics) work, as well as contributing to the development of new therapeutic strategies for rheumatic diseases.

Author affiliations

H. Takayanagi
Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.

Published online 3 November 2009