ArticleMucosal immunology2015
TNFR1-induced lethal inflammation is mediated by goblet and Paneth cell dysfunction.
Article in Mucosal immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Meta-analysis identifies the effect of dietary multi-enzyme supplementation on gut health of pigs.Scientific reports · 2021Pooled it
- Cytokine networks in Paneth cell regulation.Mucosal immunology · 2026Review
- Paneth cells as orchestrators of epithelial barrier defense and emerging therapeutic targets in inflammatory bowel disease.Seminars in immunopathology · 2026Review
- CARD14 signaling in intestinal epithelial cells induces intestinal inflammation and intestinal transit delay.EMBO molecular medicine · 2025Article
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis.The Journal of clinical investigation · 2023Article
- A platform to reproducibly evaluate human colon permeability and damage.Scientific reports · 2023Article
- Paneth cells as the cornerstones of intestinal and organismal health: a primer.EMBO molecular medicine · 2023Review
- Neutrophils and macrophages drive TNF-induced lethality via TRIF/CD14-mediated responses.Science immunology · 2022Article
- Article
- Intrarectal Capsazepine Administration Modulates Colonic Mucosal Health in Mice.International journal of molecular sciences · 2022Article
- Immunosuppressant Therapies in COVID-19: Is the TNF Axis an Alternative?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation.Nature immunology · 2022Article
- Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF.The Journal of experimental medicine · 2021Article
- Hyperglycemia minimally alters primary self-renewing human colonic epithelial cells while TNFα-promotes severe intestinal epithelial dysfunction.Integrative biology : quantitative biosciences from nano to macro · 2021Article
- Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.EMBO molecular medicine · 2020Article
- Glucocorticoids limit lipopolysaccharide-induced lethal inflammation by a double control system.EMBO reports · 2020Article
- Selective Targeting of TNF Receptors as a Novel Therapeutic Approach.Frontiers in cell and developmental biology · 2020Review
- Protective effect of extracorporeal membrane oxygenation on intestinal mucosal injury after cardiopulmonary resuscitation in pigs.Experimental and therapeutic medicine · 2019Article
- NF-κB2 signalling in enteroids modulates enterocyte responses to secreted factors from bone marrow-derived dendritic cells.Cell death & disease · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF) is a powerful activator of the immune system and a well-validated target for treatment of autoimmune diseases. Injection of TNF induces systemic lethal inflammation characterized by hypothermia, induction of multiple cytokines, and extensive damage to multiple organs. Previously, we reported that TNF-induced lethal inflammation is strictly TNFR1(P55)-dependent. We also uncovered a crucial role for P55 expression levels in intestinal epithelial cells (IECs), in which P55+/+ expression is sufficient to sensitize to TNF lethality in an otherwise fully protected P55+/- background. Here, we investigated the molecular mechanism that drives TNF toxicity in IECs. Unexpectedly, we found that the degree of TNF-induced enterocyte damage and apoptosis in IECs is equally strong in TNF-sensitive P55+/+ mice and TNF-resistant P55+/- mice. Our results suggest that P55+/+-induced signaling causes goblet and Paneth cell dysfunction, leading to severe epithelial barrier dysfunction. As a result, intestinal permeability and systemic bacterial spread are induced, causing lethal systemic inflammation. In conclusion, we identified P55-induced goblet and Paneth cell dysfunction as a crucial mechanism for TNF-induced systemic and lethal inflammation.
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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.