ArticleJournal of Crohn's & colitis2021
Gut microbial transcytosis induced by tumor necrosis factor-like 1A-dependent activation of a myosin light chain kinase splice variant contributes to IBD.
Article in Journal of Crohn's & colitis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Emergence of invasiveGut microbes · 2026Article
- The Therapeutic Potential of Targeting TL1A in a Spectrum of Inflammatory Disorders.Journal of inflammation research · 2026Review
- Elucidating the Potential Mechanism of Ulcerative Colitis Amelioration byCombinatorial chemistry & high throughput screening · 2026Article
- 5-HTThe Journal of physiology · 2025Article
- Phenotypic characterization and complete genome of a tumorigenic pathobiont Escherichia coli LI60C3.Gut pathogens · 2025Article
- TL1A as a Target in Inflammatory Bowel Disease: Exploring Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2025Review
- A Combined Therapy of Pegylated G-CSF with Ciprofloxacin Mitigates Damage Induced by Lethal Ionizing Radiation to the Bone Marrow, Spleen, and Ileum by Increasing AKT Activation but Decreasing IL-18, C3, and miR-34a.Radiation research · 2025Article
- Review
- TL1A Inhibition in Inflammatory Bowel Disease: A Pipeline Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Differential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociception.Histology and histopathology · 2024Article
- Transepithelial Barrier Dysfunction Drives Microbiota Dysbiosis to Initiate Epithelial Clock-driven Inflammation.Journal of Crohn's & colitis · 2023Article
- Protective Application of Chinese Herbal Compounds and Formulae in Intestinal Inflammation in Humans and Animals.Molecules (Basel, Switzerland) · 2023Review
- Colonic Epithelial Circadian Disruption Worsens Dextran Sulfate Sodium-Induced Colitis.Inflammatory bowel diseases · 2023Article
- The regulatory role of alternative splicing in inflammatory bowel disease.Frontiers in immunology · 2023Review
- 5-HTLaboratory investigation; a journal of technical methods and pathology · 2022Article
- MiR-128-3p alleviates TNBS-induced colitis through inactivating TRAF6/NF-κB signaling pathway in rats.The Kaohsiung journal of medical sciences · 2021Article
- A novel tumor suppressor role of myosin light chain kinase splice variants through downregulation of the TEAD4/CD44 axis.Carcinogenesis · 2021Article
- Emerging Pathological Engagement of Ferroptosis in Gut Diseases.Oxidative medicine and cellular longevity · 2021Review
- Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer.Frontiers in cellular and infection microbiology · 2021Review
- The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation.Frontiers in nutrition · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Inflammatory bowel disease (IBD) is characterized by abnormal host-microbe interactions. Proinflammatory cytokine IFNγ and a novel TNF superfamily member, TL1A, have been implicated in epithelial barrier dysfunction. The divergent regulatory mechanisms of transcellular versus paracellular hyperpermeability remain poorly understood. Intestinal epithelia express two splice variants of long myosin light chain kinase (MLCK), of which the full-length MLCK1 differ from the shorter isoform MLCK2 by a Src kinase phosphorylation site. The aim was to investigate the roles of MLCK splice variants in gut barrier defects under proinflammatory stress. Upregulated expression of TL1A, IFNγ, and two MLCK variants was observed in human IBD biopsy specimens. The presence of intraepithelial bacteria preceded tight junction (TJ) damage in dextran sodium sulfate-treated and TL1A-transgenic mouse models. Lack of barrier defects was observed in long MLCK(-/-) mice. TL1A induced MLCK-dependent terminal web (TW) contraction, brush border fanning, and transepithelial bacterial internalization. The bacterial taxa identified in the inflamed colonocytes included Escherichia, Enterococcus, Staphylococcus,and Lactobacillus. Recombinant TL1A and IFNγ at low doses induced PI3K/Akt/MLCK2-dependent bacterial endocytosis, whereas high-dose IFNγ caused TJ opening via the iNOS/Src/MLCK1 axis. Bacterial internalization was recapitulated in MLCK-knockout cells individually expressing MLCK2 but not MLCK1. Immunostaining showed different subcellular sites of phosphorylated MLC localized to the TJ and TW in the MLCK1- and MLCK2-expressing cells, respectively. In conclusion, proinflammatory cytokines induced bacterial influx through transcellular and paracellular routes via divergent pathways orchestrated by distinct MLCK isoforms. Bacterial transcytosis induced by TL1A may be an alternative route causing symptom flares in IBD.
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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.