ArticleMucosal immunology2019
Non-hematopoietic STAT6 induces epithelial tight junction dysfunction and promotes intestinal inflammation and tumorigenesis.
Article in Mucosal immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Allergen-specific T cells and clinical features of food allergy: Lessons from CoFAR immunotherapy cohorts.The Journal of allergy and clinical immunology · 2022Trial
- Intestinal epithelial cell-specific deletion of Jak2 disrupts gut homeostasis.Scientific reports · 2026Article
- Small-molecule therapies for pediatric inflammatory bowel disease: toward precision medicine.World journal of pediatrics : WJP · 2026Review
- Modified Jiaoqi powder ameliorates ulcerative colitis through gut microbiota-tryptophan metabolism-AhR signaling modulating-ILC2/ILC3 balance.Frontiers in microbiology · 2026Article
- The shifting balance: innate lymphoid cell plasticity in chronic gut diseases.Frontiers in immunology · 2026Review
- Chronic kidney disease as an active driver of digestive tract tumors: mechanistic insights and emerging management strategies.Frontiers in cell and developmental biology · 2026Review
- JAK Inhibitor and Crohn's Disease.Biomedicines · 2025Review
- STAT Signature Dish: Serving Immunity with a Side of Dietary Control.Biomolecules · 2025Review
- Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.European journal of immunology · 2025Article
- Gut‑liver axis in liver disease: From basic science to clinical treatment (Review).Molecular medicine reports · 2025Review
- STAT6 blockade ameliorates thyroid function in Graves' disease via downregulation of the sodium/iodide symporter.Endocrine connections · 2024Article
- Hexokinase 2 expression in apical enterocytes correlates with inflammation severity in patients with inflammatory bowel disease.BMC medicine · 2024Article
- Noncanonical functions of adhesion proteins in inflammation.American journal of physiology. Cell physiology · 2024Review
- Large-Scale Alternative Polyadenylation-Wide Association Studies to Identify Putative Cancer Susceptibility Genes.Cancer research · 2024Article
- A molecular subtyping associated with the cGAS-STING pathway provides novel perspectives on the treatment of ulcerative colitis.Scientific reports · 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
- Review
- Article
- Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.International journal of biological sciences · 2024Review
- Therapeutic Effects ofMicroorganisms · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhanced gut permeability due to dysregulated epithelial tight junction is often associated with inflammatory bowel diseases (IBD), which have a greater risk for developing colorectal cancer. STAT6 activation was detected in inflamed colonic epithelium of active IBD patients, suggesting a role of epithelial STAT6 in colitis development. Here, we demonstrated that non-hematopoietic STAT6, but not hematopoietic STAT6, triggered DSS-induced colitis and subsequent tumorigenesis. This could be due to the enhancing-effect of STAT6 on gut permeability and microbiota translocation via interruption of epithelial tight junction integrity. Mechanistically, long-myosin light-chain kinase (MLCK1) was identified as a target of STAT6, leading to epithelial tight junction dysfunction and microbiota-driven colitis. Furthermore, neutralization of IL-13, which was primarily derived from type 2 innate lymphoid cells (ILC2) in a microbiota-dependent way, inhibited epithelial STAT6 activation and improved gut permeability and DSS-induced colitis. Importantly, pharmacological inhibition of STAT6 reduces murine intestinal tumor formation, and tumoral p-STAT6 levels positively correlated to the clinical stage and poor prognosis of human colorectal cancer. Thus, our study reveals a direct role of STAT6 in the disruption of epithelial tight junction integrity and colitis development, and suggests STAT6 as a potential therapeutic and prophylactic target for IBD and colitis-associated cancer.
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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.