ArticleGut2002
Defining the roles of perforin, Fas/FasL, and tumour necrosis factor alpha in T cell induced mucosal damage in the mouse intestine.
Article in Gut, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 102 citations in OpenAlex.
- Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of TNature immunology · 2023Article
- Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TNature medicine · 2023Article
- Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis.Cell host & microbe · 2022Article
- Feeding mode influences dynamic gut microbiota signatures and affects susceptibility to anti-CD3 mAb-induced intestinal injury in neonatal mice.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies.Mucosal immunology · 2022Article
- Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation.Cell host & microbe · 2021Article
- JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling.Mucosal immunology · 2019Article
- The interplay between microbes and the immune response in inflammatory bowel disease.The Journal of physiology · 2018Review
- The transcriptional repressor HIC1 regulates intestinal immune homeostasis.Mucosal immunology · 2017Article
- TMucosal immunology · 2017Article
- Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Context-dependent regulation of Th17-associated genes and IFNγ expression by the transcription factor NFAT5.Immunology and cell biology · 2017Article
- Article
- Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis.Nature communications · 2015Article
- Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway.Mucosal immunology · 2015Article
- Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-γ.The Journal of experimental medicine · 2014Article
- NOD2 regulates CXCR3-dependent CD8+ T cell accumulation in intestinal tissues with acute injury.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction.PloS one · 2014Article
- Tumour necrosis factor superfamily members in the pathogenesis of inflammatory bowel disease.Mediators of inflammation · 2014Review
- p53 mediates TNF-induced epithelial cell apoptosis in IBD.The American journal of pathology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsMucosal flattening and epithelial cell apoptosis are typical features of T cell induced inflammatory diseases of the bowel, such as coeliac disease and graft versus host disease. Mice injected with a T cell activating anti-CD3 antibody develop a severe diarrhoeal illness. We describe the histological features of this enteropathy and define the effector mechanisms involved in T cell induced mucosal injury in this in vivo model.
methodsWild-type and genetically modified mice were injected with the anti-CD3 antibody 3C11 (50 microg). Changes in the murine intestine were characterised by light microscopy analysis and terminal uridine nick-end labelling (TUNEL) assay. The role of perforin, Fas/Fas ligand (FasL), tumour necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) in T cell induced mucosal damage was assessed using selected immunodeficient mouse strains.
resultsT cell activation caused severe damage, including small intestinal mucosal flattening and apoptosis of crypt epithelial cells. Mucosal damage was unaltered in anti-CD3 treated mice lacking IFN-gamma, Fas, or TNF-alpha receptors. In mice lacking TNF-alpha receptors and Fas (TNF-R1xR2 lpr/lpr strain), enterocyte apoptosis was diminished but there was no significant reduction in tissue damage. Apoptosis and mucosal injury were significantly reduced in perforin knockout mice. Abrogation of both FasL and perforin (perforin KOxgld mice) further significantly reduced tissue damage and apoptotic bodies.
conclusionsT cell induced mucosal injury is mediated by the combined effect of multiple pathways but predominantly by perforin. The redundancy of the mechanisms of tissue damage will have significant impact on therapeutic strategies aimed at specific and targeted inhibition of inflammatory processes.
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Registered trials
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