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December 8, 2025BloodOpen Access

IFNγ-driven MHC class II expression by intestinal epithelial cells dictates local cytolytic Th1 cell differentiation and intestinal stem cell loss

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Authors

AYAlbert C. YehSLSamuel R.W. LeggTSTomoko Sekiguchi

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Overview

Observational analysis shows lethal graft-versus-host disease increased by MHC class II in intestinal epithelial cells, implying critical role of IFNγ signaling.

Key Points

  • Graft-versus-host disease induces lethal gut complications, with differing survival rates in mice lacking MHC class II pre-transplant.
  • Granzyme-expressing cytolytic Th1 differentiation aligns with heightened MHC class II expression on intestinal epithelial cells.
  • IFN-γ receptor deletion on intestinal epithelial cells reduces donor T cell expansion and MHC expression, improving survival rates.
  • Study highlights the importance of the IFNγ–MHC class II axis in initial CD4+ T cell-mediated intestinal immune response.

Cite This Study

Yeh et al. (2025) studied this question.

synapsesocial.com/papers/69362f6c4fa91c937236dfb0https://doi.org/10.1182/blood-2025-159
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Galectin-3 in host murine models lessens the severity of graft-versus-host disease by preserving intestinal stem cells irrespective of gut microbiota composition2025
  2. 2Secondary lymphoid organ endothelial cells prime alloreactive CD4 + T cells to trigger acute graft-versus-host disease2025
  3. 3Monocarboxylate transporter 1 deficient donor T cells rewire metabolism and ameliorate aGVHD lethality2025
  4. 4Ornithine decarboxylase deficiency in donor T cells preserves strong GVL activity while attenuating acute and preventing steroid-resistant gut GVHD in a recipient tissue PD-L1-dependent manner2025
  5. 5Transcriptional programming by GATA3 regulates CD4+ T cell GM-CSF production in the gastrointestinal tract during graft versus host disease2025