ArticleMucosal immunology2018
Colonic epithelial mTORC1 promotes ulcerative colitis through COX-2-mediated Th17 responses.
Article in Mucosal immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Ulcerative colitis, pathophysiological mechanisms and drug repurposing: a new therapeutic dawn-narrative review.Inflammopharmacology · 2026Review
- Unraveling the pleiotropic roles of the mTOR-glycolytic axis in ulcerative colitis: from immunometabolic dysregulation to mucosal barrier remodeling.Frontiers in immunology · 2026Review
- Gut microbiota-derived metabolites and IL-22 signaling in inflammatory bowel disease: context-dependent regulation of mucosal repair and inflammation.Frontiers in immunology · 2026Review
- Metabolomics and proteomics reveal blocking argininosuccinate synthetase 1 alleviates colitis in mice.Nature communications · 2025Article
- Low Protein Diet Exacerbates Experimental Mouse Models of Colitis through Epithelial Autonomous and Nonautonomous Mechanisms.The Journal of nutrition · 2025Article
- Amphiphilic Celecoxib-Polysaccharide Delivery System for Enhanced Colon-Targeted Colitis Therapy.Pharmaceutics · 2025Article
- IgA2 ACPA Drives a Hyper-Inflammatory Phenotype in Macrophages via ATP Synthase and COX2.European journal of immunology · 2025Article
- The Oral Microbiota and Its Implications for Inflammatory Bowel Disease: A Literature Review.International journal of general medicine · 2025Review
- Targeting persistently activated inflammatory microenvironment to promote chronic wound healing.Frontiers in immunology · 2025Review
- Elevated risk of adverse effects from foodborne contaminants and drugs in inflammatory bowel disease: a review.Archives of toxicology · 2024Review
- Unveiling Immunomodulatory Effects ofJournal of microbiology and biotechnology · 2024Article
- Colitis-associated carcinogenesis: crosstalk between tumors, immune cells and gut microbiota.Cell & bioscience · 2023Review
- Article
- Hypoxia in the Pathophysiology of Inflammatory Bowel Disease.Comprehensive Physiology · 2023Article
- Analysis of Systemic Epigenetic Alterations in Inflammatory Bowel Disease: Defining Geographical, Genetic and Immune-Inflammatory influences on the Circulating Methylome.Journal of Crohn's & colitis · 2023Article
- 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid alleviates ulcerative colitis by suppressing mammalian target of rapamycin complex 1 activation and regulating intestinal microbiota.World journal of gastroenterology · 2022Article
- Molecular mechanisms of Huanglian jiedu decoction on ulcerative colitis based on network pharmacology and molecular docking.Scientific reports · 2022Article
- Article
- Article
- Exploring the Molecular Mechanism of Tong Xie Yao Fang in Treating Ulcerative Colitis Using Network Pharmacology and Molecular Docking.Evidence-based complementary and alternative medicine : eCAM · 2022Article
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The functional role of colonic epithelium in the pathogenesis of ulcerative colitis (UC) remains unclear. Here, we reveal a novel mechanism by which colonic epithelia recruit T helper-17 (Th17) cells during the onset of UC. mTOR complex 1 (mTORC1) was hyper-activated in colonic epithelia of UC mice. While colonic epithelial TSC1 (mTORC1 negative regulator) disruption induced constitutive mTORC1 activation in the colon epithelia and aggravated UC, RPTOR (essential mTORC1 component) depletion inactivated mTORC1 and ameliorated UC. TSC1 deficiency enhanced, whereas RPTOR ablation reduced the expression of cyclooxygenase 2 (COX-2), interleukin-1 (IL-1), IL-6, and IL-23, as well as Th17 infiltration in the colon. Importantly, inhibition of COX-2 reversed the elevation in the expression of these proinflammatory mediators induced by TSC1 deficiency, and subsequently reduced the symptoms and pathological characteristics of UC in mouse models. Mechanistically, mTORC1 activates COX-2 transcription via phosphorylating STAT3 and enhancing it's binding to the COX-2 promoter. Consistently, enhanced mTORC1 activity and COX2 expression, as well as strong positive correlation between each other, were observed in colonic epithelial tissues of UC patients. Collectively, our study demonstrates an essential role of epithelial mTORC1 in UC pathogenesis and establishes a novel link between colonic epithelium, Th17 responses, and UC development.
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