Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology

Sarah Unterberger, Kevin A Davies, Srinivasa Bhargav Rambhatla, Sandra Sacre Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton, BN1 9PS, UKCorrespondence: Sandra Sacre Tel +441273 872865Email s.sacre@bsms.ac.ukAbstract: Rheumatoid arthritis (RA) is a progressive autoimmune disease that is characterized by inflammation of the synovial joints leading to cartilage and bone damage. The pathogenesis is sustained by the production of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6, which can be targeted therapeutically to alleviate disease severity. Several innate immune receptors are suggested to contribute to the chronic inflammation in RA, through the production of pro-inflammatory factors in response to endogenous danger signals. Much research has focused on toll-like receptors and more recently the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 (NLRP3) inflammasome, which is required for the processing and release of IL-1β. This review summarizes the current understanding of the potential involvement of these receptors in the initiation and maintenance of inflammation and tissue damage in RA and experimental arthritis models.Keywords: rheumatoid arthritis, IL-1, IL-6, TNF, toll-like receptor, NLRP3 inflammasom