Arthritis Rheumatol. 2025 May 21.
Mucosal-associated invariant T (MAIT) cells are innate-like T cells defined by their semi-invariant T cell receptor (TCR) and restriction by the MHC class I-related molecule (MR1). These cells are primarily activated by microbial-derived metabolites presented by MR1 or by cytokines. Upon activation, MAIT cells rapidly produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-17, and secrete cytotoxic molecules such as granzyme B. Due to their ability to interact with microbiota and accumulate in inflamed tissues, MAIT cells have attracted great interest in autoimmune and inflammatory diseases. In this review, we summarize recent findings on MAIT cells in major rheumatic diseases, including rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren syndrome, and dermatomyositis. Circulating MAIT cells frequency is reduced in these diseases. Interestingly, the residual MAIT cells exhibit an activated profile and increased cytokine-producing capacity in some conditions. Moreover, an enrichment of MAIT cells in inflamed tissues is described in rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, and primary Sjögren syndrome. This pattern suggests that MAIT cells may migrate from the circulation to inflamed tissues, contributing to local immune responses. Furthermore, they have been shown to play a critical role in disease progression in two mouse models. All these findings suggest an involvement of MAIT cells in inflammatory rheumatologic diseases and their potential therapeutic target.