Journal
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
Volume 51, Issue 1, Pages 59-78Publisher
HUMANA PRESS INC
DOI: 10.1007/s12016-015-8520-9
Keywords
Rheumatoid arthritis; Osteoclasts; Osteoclast precursors; Cell migration
Categories
Funding
- NIH [RO1AI113040]
- Careers in Immunology Fellowship program of the American Association of Immunologists
- Fundacao para a Ciencia e Tecnologia (FCT, Portugal) [SFRH/BD/73782/2010]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/73782/2010] Funding Source: FCT
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Self-reactive B and T lymphocytes cooperate to promote antibody responses against self proteins and are major drivers of disease. T lymphocytes also promote RA independently of B lymphocytes mainly through the production of key inflammatory cytokines, such as IL-17, that promote pathology. While the innate signals that initiate self-reactive adaptive immune responses are poorly understood, the disease is predominantly caused by inflammatory cellular infiltration and accumulation in articular tissues, and by bone erosions driven by bone-resorbing osteoclasts. Osteoclasts are giant multinucleated cells formed by the fusion of multiple myeloid cells that require short-range signals, such as the cytokines MCSF and RANKL, for undergoing differentiation. The recruitment and positioning of osteoclast precursors to sites of osteoclast differentiation by chemoattractants is an important point of control for osteoclastogenesis and bone resorption. Recently, the GPCR EBI2 and its oxysterol ligand 7a, 25 dihydroxycholesterol, were identified as important regulators of osteoclast precursor positioning in proximity to bone surfaces and of osteoclast differentiation under homeostasis. In chronic inflammatory diseases like RA, osteoclast differentiation is also driven by inflammatory cytokines such as TNFa and IL-1, and can occur independently of RANKL. Finally, there is growing evidence that the chemotactic signals guiding osteoclast precursors to inflamed articular sites contribute to disease and are of great interest. Furthering our understanding of the complex osteoimmune cell interactions should provide new avenues of therapeutic intervention for RA.
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