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Disease progression in RA begins with asymptomatic autoimmune responses in cases with a genetic or environmental predisposition, that alters to arthralgia phase as autoantibodies reach the joints and subjects begin demonstrating nonspecific musculoskeletal presentations lacking any clinical symptoms of synovial inflammation. After that, patients' symptoms develop to undifferentiated arthritis (UA)\/idiopathic arthritis (IA) whenever the subjects progress to clinical synovitis systemic comorbidities affecting the vasculature, metabolism, and bone, and eventually with augmented immune cell infiltration, IA\/UA patients progress to clinically classifiable RA. RA is mainly correlated with different immune cells and each of them contributes variously to the pathogenesis of the disease. The pathogenesis of RA is altered by the contribution of both T and B cells in an autoimmune irregularity. Modulation of the immune responses occurs through regulatory and inhibitory molecules that control activation of the adaptive system as well as immune hemostasis. To confine the exorbitant T cell\u2010associated inflammatory reactions, the immune system provides a system of inhibitory feedbacks, collectively named immune checkpoints. In this review, we aimed to discuss about inhibitory members of immune checkpoint molecules, including programmed cell death 1 (PD\u20101)\/PD\u2010L1, cytotoxic\u2010T\u2010lymphocyte\u2010antigen\u20104,\u00a0lymphocyte activation gene\u20103, T cell immunoglobulin\u20103, V\u2010domain Ig suppressor of T cell activation, B\u2010 and T\u2010lymphocyte attenuator, and T cell immunoglobulin and ITIM domain\u00a0and their role in RA.<\/jats:p>","DOI":"10.1002\/jcp.30855","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T10:09:47Z","timestamp":1659953387000},"page":"3541-3553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The role of immune regulatory molecules in rheumatoid arthritis: Implication for etiopathogenesis and prospective for 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