1e:T513,Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.1f:T4b4,Rheumatoid arthritis is a systemic autoimmune disease, but disease flares typically affect only a subset of joints, distributed in a distinctive pattern for each patient. Pursuing this intriguing pattern, we show that arthritis recurrence is mediated by long-lived synovial resident memory T cells (T_RM). In three murine models, CD8+ cells bearing T_RM markers remain in previously inflamed joints during remission. These cells are bona fide T_RM, exhibiting a failure to migrate between joints, preferential uptake of fatty acids, and long-term residency. Disease flares result from T_RM activation by antigen, leading to CCL5-mediated recruitment of circulating effector cells. Correspondingly, T_RM depletion ameliorates recurrence in a site-specific manner. Human rheumatoid arthritis joint tissues contain a comparable CD8+-predominant T_RM population, which is most evident in late-stage leukocyte-poor synovium, exhibiting limited T cell receptor diversity and a pro-inflammatory transcriptomic signature. Together, these findings establish synovial T_RM as a targetable mediator of disease chronicity in autoimmune arthritis.

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