ArticleThe Journal of clinical investigation2022
Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 32 citations in OpenAlex.
- Integrated Necroptosis Within Programmed Cell Death in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- Microbiome-produced nicotinic acid controls colon regional identity and injury susceptibility.Cell · 2026Article
- Type I and III interferons synergize with TNF to promote virally-triggered damage to the intestinal epithelium.bioRxiv : the preprint server for biology · 2026Article
- Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- TNIP1 Impacts Prognosis by Modulating the Immune Microenvironment in BRCA.Biochemical genetics · 2026Article
- Macrophage-related GBP4 as a Novel Biomarker for Crohn's Disease: Insights from WGCNA, Mendelian Randomization, and Immunohistochemical Validation.Current topics in medicinal chemistry · 2026Article
- Bismuth subsalicylate profoundly alters gut microbiome and immunity with increased susceptibility to infection.medRxiv : the preprint server for health sciences · 2025Article
- Distinct roles for B cell-derived LTα3 and LTα1β2 in TNF-mediated ileitis.Nature immunology · 2025Article
- Diagnostic and prognostic significance of Super-enhancer-associated genes in Crohn's disease and immune regulatory roles.European journal of medical research · 2025Article
- ACSS2-Mediated Histone H4 Lysine 12 Crotonylation (H4K12cr) Alleviates Colitis via Enhancing Transcription of CLDN7.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Early subclinical stages of the inflammatory bowel diseases: insights from human and animal studies.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders.Biomedicines · 2024Review
- Leucine zipper protein 1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling.Journal of advanced research · 2024Article
- Dysregulation of CD4Journal for immunotherapy of cancer · 2024Article
- Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.Nature communications · 2024Article
- Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease.Frontiers in immunology · 2024Article
- Research progress on the relationship between Paneth cells-susceptibility genes, intestinal microecology and inflammatory bowel disease.World journal of clinical cases · 2023Review
- Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis.The Journal of clinical investigation · 2023Article
- Article
- TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis.Acta pharmacologica Sinica · 2023Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Anti-TNF antibodies are effective for treating patients with inflammatory bowel disease (IBD), but many patients fail to respond to anti-TNF therapy, highlighting the importance of TNF-independent disease. We previously demonstrated that acute deletion of 2 IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial cells (IECs) sensitized mice to both TNF-dependent and TNF-independent death. Here we show that TNF-independent IEC death after A20 and Abin-1 deletion was rescued by germ-free derivation or deletion of MyD88, while deletion of Trif provided only partial protection. Combined deletion of Ripk3 and Casp8, which inhibits both apoptotic and necroptotic death, completely protected against death after acute deletion of A20 and Abin-1 in IECs. A20- and Abin-1-deficient IECs were sensitized to TNF-independent, TNFR1-mediated death in response to lymphotoxin α (LTα) homotrimers. Blockade of LTα in vivo reduced weight loss and improved survival when combined with partial deletion of MyD88. Biopsies of inflamed colon mucosa from patients with IBD exhibited increased LTA and IL1B expression, including a subset of patients with active colitis on anti-TNF therapy. These data show that microbial signals, MyD88, and LTα all contribute to TNF-independent intestinal injury.
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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.