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May 25, 2025Mucosal ImmunologyOpen Access

MAIT cells exacerbate colonic inflammation in a genetically diverse murine model of spontaneous colitis

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Authors

LLLiyen LohDODavid J. OrlickyASAndrea Spengler

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Overview

Murine study demonstrates that MAIT cells drive chronic colonic inflammation in genetically prone mice, indicating that targeting mucosal-associated invariant T cells may alleviate colitis.

Key Points

  • To elucidate the pathogenic role and regulatory cues of mucosal-associated invariant T (MAIT) cells in spontaneous chronic intestinal inflammation.
  • Characterized mucosal immune profiles and intestinal permeability in the spontaneous chronic colitis mouse model CC011/Unc.
  • Profiled colonic MAIT cells using single-cell transcriptomics and tested MR1-dependent activation using CC011 microbiota.
  • Generated CC011 mice lacking Traj33 to evaluate the impact of MAIT cell deficiency on colonic disease.
  • Colonic MAIT cells expanded alongside age-dependent intestinal barrier loss and adopted a pathogenic Th17-like profile expressing IL-17A, IFNγ, and IL-23R.
  • CC011-derived microbiota stimulated MR1-dependent MAIT cell activation and facilitated MAIT17 accumulation in peripheral tissues.
  • Targeted deletion of Traj33 prevented MAIT cell development and significantly reduced colonic inflammation.

Cite This Study

Loh et al. (2025) studied this question.

synapsesocial.com/papers/6a719525febe604dd70a2dbehttps://doi.org/10.1016/j.mucimm.2025.05.006
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