Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.
Highlights
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease causing progressive joint damage that can lead to lifelong disability [1]
tumor necrosis factor (TNF) controls affects the function and by differentiation of T regulatory (Treg) cells, which are essential for been shown that hypomethylation is associated with increased gene expression, and that maintenance of immune homeostasis and prevention of autoimmunity, and whose differmany genes involved in RA pathogenesis, including signal transducer and activator of transcription 3 (STAT3) and TNF receptor associated factor (TRAF)2, are hypomethylated in synovial fibroblasts derived from RA patients [38]
Based on the rationale that TNF-α plays a central role in the regulation of RA-related molecules, anti-TNF drugs were the first biological agents to be introduced for treatment of RA, starting with infliximab, a chimeric anti-TNF-α monoclonal antibody, in 1999 [1,17]
Summary
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease causing progressive joint damage that can lead to lifelong disability [1]. ACPA and RF form immune complexes with citrullinated proteins and activate macrophages, triggering the release of inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 [7]. Proinflammatory cytokines such as TNF, IL-6, and to IL-17 actigranulocyte macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase (MMPs), leading enrichment vate synovial fibroblasts, secrete various molecules including. Various signals such as IL-2 from T helper (Th) 17 cells, IL-7 from inflamed tissue, and IL-33 from These stimuli induce receptor activator of NF-κB ligand (RANKL) on fibroblasts and induce osteoclasts from extrinsic or endothelium or synovial fibroblasts can activate group 2 innate lymphoid cells (ILC2) to release GM-CSF. Those with the most potential include escape from or control of environmental stimuli, inhibitors of cytokines other than TNF and IL-6, a specific stimulator of TNF receptor 2 (TNFR2), and a PAD inhibitor
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