ArticleMucosal immunology2014
Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis.
Article in Mucosal immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 156 citations in OpenAlex.
- Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response.Cell reports. Medicine · 2024Trial
- Evaluation of Toltrazuril and Sulfaclozine resistance in chicken coccidiosis in Vietnam and its impact on intestinal recovery.Veterinary research communications · 2026Article
- Intestinal epithelial cell-specific deletion of Jak2 disrupts gut homeostasis.Scientific reports · 2026Article
- Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.Laboratory investigation; a journal of technical methods and pathology · 2026Article
- Integrated transcriptomic and functional characterization of Claudin-1 reveals its oncogenic and immunomodulatory roles in pancreatic ductal adenocarcinoma.Tissue barriers · 2026Article
- Dietary Flavonoids as Cross-System Modulators of Hypertension and Intestinal Permeability.Molecules (Basel, Switzerland) · 2025Review
- Exploring the interplay betweenThe veterinary quarterly · 2025Review
- The septin cytoskeleton is a regulator of intestinal epithelial barrier integrity and mucosal inflammation.JCI insight · 2025Article
- Indole-3-lactic acid protects the gut vascular barrier following intestinal ischemia injury through AhR/Nrf2/STAT3 mediated claudin 2 downregulation.Cell communication and signaling : CCS · 2025Article
- Article
- Galactooligosaccharides Promote Gut Barrier Integrity and Exert Anti-Inflammatory Effects in DSS-Induced Colitis Through Microbiota Modulation.International journal of molecular sciences · 2025Article
- Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia.Cancer research communications · 2025Article
- Modeling ETBF-Mediated Colorectal Tumorigenesis Using AOM/DSS in Wild-Type Mice.International journal of molecular sciences · 2025Article
- Functional maturation of preterm intestinal epithelium through CFTR activation.Communications biology · 2025Article
- Importance of rectal over colon status in ulcerative colitis remission: the role of microinflammation and mucosal barrier dysfunction in relapse.Journal of gastroenterology · 2025Article
- Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways.Inflammatory bowel diseases · 2025Review
- Tight junction regulation, intestinal permeability, and mucosal immunity in gastrointestinal health and disease.Current opinion in gastroenterology · 2025Review
- Effect of chronic heat stress on duodenal epithelial barrier integrity in low- and high-water-efficient broiler chickens.Frontiers in physiology · 2025Article
- Protective Capacity ofPharmaceuticals (Basel, Switzerland) · 2024Article
- The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin.Biomolecules · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Expression of claudin-2, a tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Notably, claudin-2 has also been implicated in the regulation of intestinal epithelial proliferation. However, precise role of claudin-2 in regulating colonic homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic mice, that increased colonic claudin-2 expression augments mucosal permeability as well as colon and crypt length. Most notably, despite leaky colon, Cl-2TG mice were significantly protected against experimental colitis. Importantly, claudin-2 expression increased colonocyte proliferation and provided protection against colitis-induced colonocyte death in a PI-3Kinase/Bcl-2-dependent manner. However, Cl-2TG mice also demonstrated marked suppression of colitis-induced increases in immune activation and associated signaling, suggesting immune tolerance. Accordingly, colons from naive Cl-2TG mice harbored significantly increased numbers of regulatory (CD4(+)Foxp3(+)) T cells than WT littermates. Furthermore, macrophages isolated from Cl-2TG mouse colon exhibited immune anergy. Importantly, these immunosuppressive changes were associated with increased synthesis of the immunoregulatory cytokine TGF-β by colonic epithelial cells in Cl-2TG mice compared with WT littermates. Taken together, our findings reveal a critical albeit complex role of claudin-2 in intestinal homeostasis by regulating epithelial permeability, inflammation and proliferation and suggest novel therapeutic opportunities.
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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.