Emerging Roles of Mucosal-Associated Invariant T Cells in Rheumatology

Abstract

Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset expressing a semi-invariant TCR and recognize microbial riboflavin metabolites presented by major histocompatibility complex class 1-related molecule (MR1). MAIT cells serve as innate-like T cells bridging innate and adaptive immunity, which have attracted increasing attention in recent years. The involvement of MAIT cells has been described in various infections, autoimmune diseases and malignancies. In this review, we first briefly introduce the biology of MAIT cells, and then summarize their roles in rheumatic diseases including systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren’s syndrome, psoriatic arthritis, systemic sclerosis, vasculitis and dermatomyositis. An increased knowledge of MAIT cells will inform the development of novel biomarkers and therapeutic approaches in rheumatology.

In patients with primary Sjögren’s syndrome innate-like MAIT cells display upregulated IL-7R, IFN-γ, and IL-21 expression and have increased proportions of CCR9 and CXCR5-expressing cells

“…In accordance with earlier work, we found that in pSS patients the number of CD4 MAIT cells is elevated as compared to controls ( 48 ). Our data corroborate previous studies demonstrating that as compared to CD3 T cells MAIT cells have a strongly skewed CD4/CD8 T cell ratio with skewing towards CD8 T cells ( 28 , 35 , 41 , 42 ). Here we demonstrate that for both CD161 and IL-18Rα-expressing MAIT cells in pSS patients this is even further skewed.…”

“…MAIT cells are activated both in TCR-dependent and TCR-independent ways, including stimulation by IL-7, IL-12, and IL-18 ( 37 – 40 ). In humans MAIT cells predominantly express CD8, or express neither CD8 nor CD4 ( ± 70-80% and ±15%, respectively), and just a few percent of MAIT cells express CD4 ( 28 , 35 , 41 , 42 ). MAIT cells can be identified in blood and tissues based on the expression of CD3 and TCRVα7.2 in combination with either CD161 and/or IL-18Rα ( 32 , 35 , 43 ).…”

Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?

“…Recent work in respiratory diseases, rheumatic diseases, and endocrine diseases similarly revealed versatile effects of MAIT cells, raising questions on their respective effects and suggesting that the role of MAIT cells may largely vary depending on disease and context in the tissue. 15 , 116 , 117 , 118 Overall, the functions of MAIT cells in various diseases remain largely elusive and more work is needed to define the molecular mechanisms that underlie their variable functions.…”

“… 4 , 13 Peripheral blood MAIT cells express different combinations of chemokine receptors that mediate the migration of MAIT cells to peripheral tissues, including the gut-homing chemokine receptors α4β7 and CCR9, and the receptors CCR6 and CXCR6 involved in hepatic homing. 14 , 15 , 16 , 17 CD161 is often used in conjunction with Va7.2 as a marker for MAIT cells. 18 However, CD161 is expressed by non-MAIT cells in human tissues.…”

Emerging story of gut dysbiosis in spondyloarthropathy: From gastrointestinal inflammation to spondyloarthritis

“…Other immune cells, including mast cells and macrophages, can further amplify the inflammatory effect by secreting cytokines such as IL-23, IL-17, IL-1, IL-22, and tumor necrosis factor (TNF)-α ( Annunziato et al., 2015 ). MAIT cells are capable of producing pro-inflammatory cytokines, such as IL-17, IL-22, TNF, or interferon (IFN)-γ ( Gracey et al., 2016 ; Toussirot and Saas, 2018 ; Li et al., 2022 ). Taken together, these findings show that various immune cell-mediated IL-23/IL-17 axes contribute to the migration of blood vessels.…”