Pathogenesis of rheumatoid arthritis. Part II – innate immunity, new therapeutic targets

Chronic inflammation of synovial membrane and hyperplasia of intimal lining, which transforms into the invasive tissue – pannus, are characteristic features of rheumatoid arthritis (RA). Fibroblast-like (FLS) and macrophage-like (MfLS) synoviocytes are cellular components of intimal lining. The architecture of this layer is established by FLS, while both types of synoviocytes form niches for infiltrating cells as well as represent the major source of locally synthesized proinflammatory factors and connective tissue degrading enzymes. Abnormal blood vessels’ formation and massive infiltration of subsynovium by acquired and innate immune cells results in synovial hypoxia. Due to the action of numerous stimulating factors, synoviocytes and innate immune cells are kept in the activation state, and continuously support inflammatory response and tissue destructive processes. The most important reports on the role of these cells in RA pathogenesis are discussed, summarized and illustrated on the figure. Progress in the research on this subject allows for new therapeutic procedures to be developed and some of them are currently tested in clinical trials. This issue is also reviewed in the paper. The role of cytokines and destruction of joint cartilage and bone will be described in the next review article (the last article in the series concerning pathogenesis of RA).