Rheumatoid Arthritis (RA) is a persistent autoimmune inflammatory disorder that arises from the intricate interaction between genetic predisposition and environmental influences. The progression of RA can be delineated into four distinct phases: initially, the influence of genetic and environmental risk factors
followed by the emergence of systemic autoimmunity
subsequently, an asymptomatic inflammatory phase
and ultimately, the manifestation of clinical arthritis. Recently, the role of mucosal immunity in RA has gained significant attention in research. Evidence from published studies suggests that mucosal immunity not only influences the onset of RA but also plays a crucial role in its progression. Scholars have begun to unravel the intricate links between RA and the mucosal barriers of the gastrointestinal tract, respiratory system, and oral cavity. Specifically, shifts in the mucosal microbiota, dysfunction of mucosal barriers, and the abnormal activation of mucosal immune tissues are all implicated in the pathogenesis of RA.Despite this growing body of knowledge, a comprehensive review of the abnormal mucosal immunity in RA and its therapeutic implications is yet to be conducted. This review emphasizes the driving role of mucosal immune abnormalities in the development of systemic autoimmunity in rheumatoid arthritis (RA). It further explores the therapeutic potential of mucosal immunity in RA, as well as the issues and challenges that need to be addressed in the current research field, providing a new perspective and potential therapeutic targets for the prevention and treatment of RA.