Autoimmune arthritis: the interface between the immune system and joints

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic inflammation and synovial hyperplasia in the joints that ultimately lead to cartilage and bone destruction. A wealth of research has shown that CD4(+) T cells, especially IL-17 producing helper T (Th17) cells, play an important role in RA development. However, it still remains to be clarified how the systemic immune response results in the local joint disorders. Studies on animal models of RA have shed light on the importance of the interaction between immune cells and joint-specific mesenchymal cells. In particular, joint-specific mesenchymal cells contribute to the Th17-mediated augmentation of the inflammatory phase in RA by promoting the migration of Th17 cells to the inflammatory joint and then homeostatic proliferation with increase in IL-17 production. In addition, recent progress in osteoimmunology has provided new insights into the pathogenesis of the bone destruction phase in RA. Of note, Th17 cells have been shown to enhance the differentiation of osteoclasts via joint-specific mesenchymal cells. Thus, the interaction of CD4(+) T cells and nonhematopoietic mesenchymal cells in joints plays a key role in RA pathogenesis during both the inflammatory and bone destruction phases. Focusing on this interaction will lead to a better understanding of the mechanism by which the systemic immune response results in local joint disorders and also helps provide a molecular basis for novel therapeutic strategies.