bims-maitce Biomed News
on MAIT cells
Issue of 2025–05–18
four papers selected by
Andy E. Hogan, Maynooth University



  1. J Rheumatol. 2025 May 15. pii: jrheum.2024-1294. [Epub ahead of print]
       OBJECTIVE: mucosal-associated invariant T cells (MAIT) have been involved in the pathophysiology of axial spondyloarthritis (axSpA). We aimed to further investigate the phenotype of circulating MAIT cells in patients with axSpA by assessing the expression of an activation marker and gut homing receptors as well as the impact of TNF-α blockade. The presence of MAIT cells in synovial biopsies from axSpA patients was also studied.
    METHODS: blood samples were obtained from 26 axSpA patients (11 radiographic, 15 nonradiographic) and 27 healthy controls (HC). Frequency of Vα7.2+CD161+ MAIT cells was determined in axSpA and HC. Expression of CD69, CCR9 and CD49d on MAIT cells was analyzed by flow cytometry. The presence of MAIT cells was examined in synovial biopsy samples from three axSpA patients and compared to synovial biopsies from 3 rheumatoid arthritis (RA) patients and 4 osteoarthritis (OA) patients by confocal microscopy.
    RESULTS: patients with axSpA were characterized by a higher frequency of CD3+ and CD8+ MAIT cells expressing CD69, CCR9 and CD49d, especially in the radiographic subgroup. MAIT cells were detected in a synovial biopsy sample from one patient with axSpA. After TNF-α blockade, a decrease in the frequency of MAIT cells and TNF-α/IL-17A - producing-MAIT cells was observed.
    CONCLUSION: MAIT cells were activated and expressed gut homing receptors, indicating their potential involvement in the gut-joint axis of axSpA. MAIT cell frequency and function were reduced by TNF-α blockade. MAIT cells could be found in synovial tissue in axSpA.
    DOI:  https://doi.org/10.3899/jrheum.2024-1294
  2. Hepatol Commun. 2025 Jun 01. pii: e0714. [Epub ahead of print]9(6):
       BACKGROUND: Mucosal-associated invariant T (MAIT) cells are diminished in various liver diseases, but the underlying mechanism remains unclear. This study aimed to investigate the characteristics and underlying mechanisms of MAIT cell depletion in HBV-related cirrhosis.
    METHODS: Peripheral blood samples were collected from 20 healthy controls and 40 patients with HBV-related cirrhosis, divided into compensated (20) and decompensated (20) liver cirrhosis groups. Flow cytometry, single-cell RNA sequencing (scRNA-seq), multiplex immunofluorescence, and ELISA were used to assess MAIT cell characteristics.
    RESULTS: In patients with HBV-related cirrhosis, MAIT cells were significantly reduced and hyperactivated. The levels of pyroptosis and oxidative stress were elevated, particularly in those with decompensated liver cirrhosis (DLC). As disease severity increased, both pyroptosis and oxidative stress in MAIT cells rose, negatively correlating with MAIT cell frequency. Additionally, MAIT cells from patients with compensated liver cirrhosis (CLC) and DLC had lower levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granzyme B (GZMB), and CD107a, but higher IL-17A levels. Blocking IL-12 and IL-18 pathways reduced MAIT cell activation and pyroptosis, while antioxidants effectively decreased pyroptosis in vitro.
    CONCLUSIONS: Pyroptosis contributes to the decline of MAIT cells in HBV-related cirrhosis, while antioxidants can reduce this process.
    Keywords:  HBV-related cirrhosis; antioxidant; cytokines pyroptosis; mucosal-associated invariant T cell
    DOI:  https://doi.org/10.1097/HC9.0000000000000714
  3. Front Immunol. 2025 ;16 1569915
      Metabolic dysfunction-associated steatotic liver disease (MASLD) is a series of obesity-related metabolic liver diseases, ranging from relatively benign hepatic steatosis to metabolic-associated steatohepatitis (MASH). With the changes in lifestyle, its incidence and prevalence have risen to epidemic proportions globally. In recent years, an increasing amount of evidence has indicated that the hepatic microenvironment is involved in the pathophysiological processes of MASH-induced liver fibrosis and the formation of hepatocellular carcinoma (HCC). The hepatic microenvironment is composed of various parenchymal and non-parenchymal cells, which communicate with each other through various factors. In this review, we focus on the changes in hepatocytes, cholangiocytes, liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), Kupffer cells (KC), dendritic cells (DC), neutrophils, monocytes, T and B lymphocytes, natural killer cells (NK), natural killer T cells (NKT), mucosal-associated invariant T cells (MAIT), γδT cells, and gut microbiota during the progression of MASLD. Furthermore, we discuss promising therapeutic strategies targeting the microenvironment of MASLD-MASH-HCC.
    Keywords:  HCC; MASH; MASLD; microenvironment; therapeutics
    DOI:  https://doi.org/10.3389/fimmu.2025.1569915
  4. Proc Natl Acad Sci U S A. 2025 May 20. 122(20): e2418525122
      Mitochondria coordinate several metabolic pathways, producing metabolites that influence the immune response in various ways. It remains unclear whether mitochondria impact antigen presentation by the MHC-class-I-related antigen-presenting molecule, MR1, which presents small molecules to MR1-restricted T-lymphocytes. Here, we demonstrate that mitochondrial complex III and the enzyme dihydroorotate dehydrogenase are essential for the cell-surface expression of MR1 and for generating uridine- and thymidine-related compounds that bind to MR1 and are produced upon oxidation by reactive oxygen species. One mitochondria-derived immunogenic formylated metabolite we identified is 5-formyl-deoxyuridine (5-FdU). Structural studies indicate that 5-FdU binds in the A'-antigen-binding pocket of MR1, positioning the deoxyribose toward the surface of MR1 for TCR interaction. 5-FdU stimulates specific T cells and detects circulating T cells when loaded onto MR1-tetramers. 5-FdU-reactive cells resemble adaptive T cells and express the phenotypes of naïve, memory, and effector cells, indicating prior in vivo stimulation. These findings suggest that mitochondria may play a role in MR1-mediated immune surveillance.
    Keywords:  MR1; T cells; antigen presentation; formylated metabolite; mitochondria
    DOI:  https://doi.org/10.1073/pnas.2418525122