ArticleThe Journal of clinical investigation2023
Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 31 citations in OpenAlex.
- Loss of ST8SIA6 is associated with enhanced MUC16-Integrin β4 signaling and aggressive phenotypes in colorectal cancer.Biochemistry and biophysics reports · 2026Article
- Stress-relaxing granular bioprinting materials enable complex and uniform organoid self-organization.Nature materials · 2026Article
- TNFα signaling in radiation-induced chronic bowel dysfunction suggests therapeutic potential for IBD biologics.Molecular medicine (Cambridge, Mass.) · 2026Article
- Article
- Comprehensive analysis of heterogeneity and cell-cell interactions in Crohn's disease reveals novel location-specific insights.Journal of advanced research · 2025Article
- Stress relaxing granular bioprinting materials enable complex and uniform organoid self-organization.bioRxiv : the preprint server for biology · 2025Article
- Palmitic Acid Esterification Boosts Epigallocatechin Gallate's Immunomodulatory Effects in Intestinal Inflammation.Biomolecules · 2025Article
- The function of chloride channels in digestive system disease (Review).International journal of molecular medicine · 2025Review
- Mast cells-intestinal cancer cells crosstalk is mediated by TNF-alpha and sustained by the IL-33/ST2 axis.Cancer immunology, immunotherapy : CII · 2025Article
- Uncovering the therapeutic potential of anti-tuberculoid agent Isoniazid in a model of microbial-driven Crohn's disease.Journal of Crohn's & colitis · 2025Article
- Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease.Scientific reports · 2025Article
- Establishment of anMethodsX · 2024Article
- Challenges and opportunities in inflammatory bowel disease: from current therapeutic strategies to organoid-based models.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Control of Intestinal Stemness and Cell Lineage by Histone Variant H2A.Z Isoforms.Molecular and cellular biology · 2024Article
- Tongxieyaofang Decotion Alleviates IBS by Modulating CHRM3 and Gut Barrier.Drug design, development and therapy · 2024Article
- Bioaccessible Sulforaphane Drives Macrophage Migration and Differentiation by Reprogramming the Interleukin Profile in Intestinal Inflammation.BioFactors (Oxford, England)Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. We found that inhibition of epithelial TNF promotes the differentiation of secretory progenitor cells into mucus-producing goblet cells. Furthermore, TNF treatment and CFTR inhibition in intestinal organoids demonstrated that TNF promotes ion transport and luminal flow via CFTR. The absence of TNF led to slower gut transit times, which we propose results from increased mucus accumulation coupled with decreased luminal fluid pumping. These findings point to a TNF/CFTR signaling axis in the adult intestine and identify epithelial cell-derived TNF as an upstream regulator of mucin homeostasis.
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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.