ArticleScience immunology2019
T cell-derived interferon-γ programs stem cell death in immune-mediated intestinal damage.
Article in Science immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 150 citations in OpenAlex.
- Trial
- Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.Nature immunology · 2026Article
- The effects of IFNγ on tissue physiology through structural cells.Nature reviews. Immunology · 2026Review
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Postnatal outcomes of in utero repair of simple gastroschisis in an ovine model.Journal of pediatric surgery · 2026Article
- The roles and heterogeneity of CD8International journal of molecular medicine · 2026Review
- Tetrameric STAT5 regulates the formation of immune niche cells to protect stem cell regenerative repair against mucosal inflammation.Experimental & molecular medicine · 2026Article
- Maladaptive Inflammatory Signaling in Old Mice Impairs Colonic Regeneration by Promoting a Sustained Fetal-Like Epithelial State.Aging cell · 2026Article
- Differential effects of GVHD therapies on intestinal epithelium.Blood advances · 2026Article
- JAK inhibitors alleviate EGFR-inhibitor-induced diarrhea by protecting intestinal stem cells from adaptive-immune-exacerbated injury.Nature communications · 2026Article
- T-Cell Profiles in HBV Functional Cure and People Living With HIV: Known Knowns, Known Unknowns, and Unknown Unknowns.Current HIV/AIDS reports · 2026Review
- Organoid-Immune Co-Cultures: A Next-Generation approach to disease modeling.Molecular biology reports · 2026Review
- Parabiosis, Assembloids, Organoids (PAO).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Novel approaches for separating graft-versus-leukemia effects from graft-versus-host disease.Frontiers in oncology · 2026Review
- Bidirectional Crosstalk Between Intestinal Epithelium and Immune Microenvironment in Inflammatory Bowel Disease: Mechanisms and Therapeutic Implications.Journal of inflammation research · 2026Review
- Mast Cells Inhibit Stem Cell-driven Epithelial Repair in Inflammatory Bowel Disease via Suppressing Wnt/lrp6/β-Catenin Signaling Pathway.Cellular and molecular gastroenterology and hepatology · 2026Article
- Loss of GLP-2R signaling in Glp2rMolecular metabolism · 2026Article
- How stem cells respond to infection, inflammation and ageing.Nature reviews. Immunology · 2025Review
- Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury.Signal transduction and targeted therapy · 2025Article
- The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.Nature communications · 2025Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
Abstract
Despite the importance of intestinal stem cells (ISCs) for epithelial maintenance, there is limited understanding of how immune-mediated damage affects ISCs and their niche. We found that stem cell compartment injury is a shared feature of both alloreactive and autoreactive intestinal immunopathology, reducing ISCs and impairing their recovery in T cell-mediated injury models. Although imaging revealed few T cells near the stem cell compartment in healthy mice, donor T cells infiltrating the intestinal mucosa after allogeneic bone marrow transplantation (BMT) primarily localized to the crypt region lamina propria. Further modeling with ex vivo epithelial cultures indicated ISC depletion and impaired human as well as murine organoid survival upon coculture with activated T cells, and screening of effector pathways identified interferon-γ (IFNγ) as a principal mediator of ISC compartment damage. IFNγ induced JAK1- and STAT1-dependent toxicity, initiating a proapoptotic gene expression program and stem cell death. BMT with IFNγ-deficient donor T cells, with recipients lacking the IFNγ receptor (IFNγR) specifically in the intestinal epithelium, and with pharmacologic inhibition of JAK signaling all resulted in protection of the stem cell compartment. In addition, epithelial cultures with Paneth cell-deficient organoids, IFNγR-deficient Paneth cells, IFNγR-deficient ISCs, and purified stem cell colonies all indicated direct targeting of the ISCs that was not dependent on injury to the Paneth cell niche. Dysregulated T cell activation and IFNγ production are thus potent mediators of ISC injury, and blockade of JAK/STAT signaling within target tissue stem cells can prevent this T cell-mediated pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.