bims-maitce Biomed News
on MAIT cells
Issue of 2025–12–07
two papers selected by
Andy E. Hogan, Maynooth University
  1. Macrophage MR1 antigen presentation promotes MAIT cell immunity and lung microbiota modulation.
  2. Immune Checkpoint Expression in Mucosal-Associated Invariant T (MAIT) Cells is Stimulus-Dependent.
  1. Science. 2025 Dec 04. eadr6322
    Macrophage MR1 antigen presentation promotes MAIT cell immunity and lung microbiota modulation.
    Jieru Deng, Yuting Yan, Xiaoyue Zhang, Calum J Walsh, Emmanuel Montassier, Debajyoti Sinha, Huimeng Wang, Atieh Mousavizadeh, Mitra Ashayeripanah, Jeffrey Y W Mak, Hui-Fern Koay, Tobias Poch, Yannick O Alexandre, Scott N Mueller, Ajithkumar Vasanthakumar, Tim P Stinear, Vanta J Jameson, Alexis Perez-Gonzalez, Jenny Kingham, Tri Giang Phan, Nikita Potemkin, Lachlan Dryburgh, Jan Schroeder, David P Fairlie, Laura K Mackay, Zhenjun Chen, Laura Cook, Abderrahman Hachani, Alexandra J Corbett, Antoine Roquilly, Jose A Villadangos, Hamish E G McWilliam.
      Mucosal associated invariant T (MAIT) cells mediate tissue homeostasis and antimicrobial immunity. However, the cells that express MHC class I-related protein 1 (MR1) and present microbial vitamin B-derived antigens (VitBAg) to MAIT cells remain unknown. We found that MR1 expression varied across tissues and cell types. Macrophages from the lung and peritoneal cavity expressed the highest levels of MR1 and were the most efficient at capturing and presenting VitBAg to MAIT cells. Expression of MR1 in macrophages was regulated transcriptionally and induced by the tissue environment and microbiota. Depletion of MR1 in macrophages, dendritic cells and monocytes changed the composition of the microbiota and impaired MAIT cell responses against bacterial infection. We concluded that macrophages are key for MR1 antigen presentation and MAIT cell immunity.
    DOI:  https://doi.org/10.1126/science.adr6322
  2. J Leukoc Biol. 2025 Dec 06. pii: qiaf177. [Epub ahead of print]
    Immune Checkpoint Expression in Mucosal-Associated Invariant T (MAIT) Cells is Stimulus-Dependent.
    Christy Clutter, Audrey Re, Kenadee Jacobson, Kendell Clement, Jeffrey Aubé, Ryan M O'Connell, Daniel T Leung.
      Mucosal-associated invariant T (MAIT) cells are unique unconventional T cells with diverse roles in immunity, yet how their context informs their function is not well known. This contextual regulation is particularly relevant in cancer, where MAIT cells have an enigmatic role. We performed a systematic review and meta-analysis to identify MAIT cell transcriptomic signatures under different environmental conditions. We identified four bulk-RNA-sequencing studies that compared multiple activation stimuli. We found a stimulus-specific transcriptional signature for immune checkpoint genes, that we confirmed in a single-cell RNA-sequencing dataset. We used flow cytometry to examine in vitro human MAIT cells across four activation stimuli and confirmed that stimulus drives unique checkpoint signatures upon MAIT activation for Lag3, PD-L1, PD-1, NKG2A and Tigit. Strikingly, PD-L1 was more highly induced in vitro than PD-1 in MAIT cells up to 72 hours. Our data suggest that human MAIT cell regulation is context-dependent. These findings have the potential to critically inform efforts targeting MAIT cells for cancer immunotherapy.
    Keywords:  Cancer; Checkpoint; Immunotherapy; MAIT
    DOI:  https://doi.org/10.1093/jleuko/qiaf177
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