Mucosal-Associated Invariant T Cells in Rheumatic Diseases

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells defined by their semi-invariant T cell receptor and restriction by the major histocompatibility complex 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 proinflammatory cytokines, including interferon-γ, tumor necrosis factor α, and interleukin-17, and secrete cytotoxic molecules, such as granzyme B. Because of 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 (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), systemic lupus erythematosus, systemic sclerosis, primary Sjögren disease (pSD), and dermatomyositis. Circulating MAIT cell 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 RA, SpA, PsA, and pSD. This pattern suggests that MAIT cells may migrate from 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.