Tissue microenvironment dictates inflammation and disease activity in rheumatoid arthritis

The recent advance in treatments for rheumatoid arthritis (RA) has significantly improved the prognosis of RA patients. However, these novel therapies do not work well for all RA patients. The unmet need suggests that the current understanding about how inflammatory response arises and progresses in RA is limited. Recent accumulating evidence reveals an important role for the tissue microenvironment in the pathogenesis of RA. The synovium, the main tissue where the RA activity occurs, is composed by a unique extracellular matrix (ECM) and residing cells. The ECM molecules provide environmental signals that determine programmed site-specific cell behavior. Improved understanding of the tissue microenvironment, especially how the synovial architecture, ECM molecules, and site-specific cell behavior promote chronic inflammation and tissue destruction, will enhance deciphering the pathogenesis of RA. Moreover, in-depth analysis of tissue microenvironment will allow us to identify potential therapeutic targets. Research is now undertaken to explore potential candidates, both cellular and ECM molecules, to develop novel therapies. This article reviews recent advances in knowledge about how changes in cellular and ECM factors within the tissue microenvironment result in propagation of chronic inflammation in RA.