ArticleInflammatory bowel diseases2020
The JAK-Inhibitor Tofacitinib Rescues Human Intestinal Epithelial Cells and Colonoids from Cytokine-Induced Barrier Dysfunction.
Article in Inflammatory bowel diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Inflammatory bowel disease therapeutics: a bibliometric analysis of tofacitinib research in ulcerative colitis.Frontiers in pharmacology · 2025Pooled it
- IL-10-STAT3 axis preserves epithelial mitochondrial homeostasis during bacterial challenge.Gut microbes · 2026Article
- Patient-derived intestinal organoids in pediatric inflammatory bowel disease: applications in disease modeling and therapeutic response prediction.Clinical and experimental pediatrics · 2026Article
- Effect and Mechanisms of Electroacupuncture on Mucosal Healing in Ulcerative Colitis Mice via Non-neuroronal Cholinergic System.Chinese journal of integrative medicine · 2026Article
- Selective modulation of IL-6/JAK/STAT-related signaling under redox-shift conditions by luteolin.Molecular biology reports · 2026Article
- Microbiome-produced nicotinic acid controls colon regional identity and injury susceptibility.Cell · 2026Article
- Gut Luminal Exosomes in Young and Old Mice: Multi-Omic Characteristics and Regulation of Gut Permeability.Aging cell · 2026Article
- Odevixibat ameliorates high-fat diet-induced MASLD in mice by targeting the gut microbiota-metabolite axis and enhancing gut-liver crosstalk.Journal of physiology and biochemistry · 2026Article
- Function of the large intestine and its interaction with the brain after ischemic stroke: a comprehensive literature review.Frontiers in cellular neuroscience · 2026Review
- Deletion of Circadian Rhythms Gene BMAL1 Impairs the Intestinal Epithelial Barrier and Exacerbates Intestinal Inflammation by Inducing Pyroptosis.Mediators of inflammation · 2026Article
- Targeting macrophage JAK3/STAT3 signaling with tectochrysin: a novel therapeutic strategy to ameliorate bone erosion and synovitis in rheumatoid arthritis.Journal of orthopaedic surgery and research · 2025Article
- TheGut microbes · 2025Article
- Growth differentiation factor 15 alters intestinal barrier and increases permeability: A new molecular target in inflammatory bowel disease.World journal of gastroenterology · 2025Article
- EngineeredActa pharmaceutica Sinica. B · 2025Article
- Restoration of colonic barrier function by tofacitinib in experimental colitis: anti-inflammatory effects and decreased expression of claudins-2 and claudin-15.Intestinal research · 2025Article
- Article
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling.Antioxidants (Basel, Switzerland) · 2025Article
- Elevated SPARC Disrupts the Intestinal Barrier Integrity in Crohn's Disease by Interacting with OTUD4 and Activating the MYD88/NF-κB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Non-invasive in vitro NAM for the detection of reversible and irreversible eye damage after chemical exposure for GHS classification purposes (ImAi).Archives of toxicology · 2025Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAlterations to epithelial tight junctions can compromise the ability of the epithelium to act as a barrier between luminal contents and the underlying tissues, thereby increasing intestinal permeability, an early critical event in inflammatory bowel disease (IBD). Tofacitinib (Xeljanz), an orally administered pan-Janus kinase (JAK) inhibitor, was recently approved for the treatment of moderate to severe ulcerative colitis. Nevertheless, the effects of tofacitinib on intestinal epithelial cell functions are largely unknown. The aim of this study was to determine if JAK inhibition by tofacitinib can rescue cytokine-induced barrier dysfunction in intestinal epithelial cells (IECs).
methodsT84 IECs were used to evaluate the effects of tofacitinib on JAK-signal transducer and activator of transcription (STAT) activation, barrier permeability, and expression and localization of tight junction proteins. The impact of tofacitinib on claudin-2 promoter activity was assessed in HT-29 IECs. Tofacitinib rescue of barrier function was also tested in human colonic stem cell-derived organoids.
resultsPretreatment with tofacitinib prevented IFN-γ-induced decreases in transepithelial electrical resistance (TER) and increases in 4 kDa FITC-dextran permeability (FD4), partly due to claudin-2 transcriptional regulation and restriction of ZO-1 rearrangement at tight junctions. Although tofacitinib administered after IFN-γ challenge only partially normalized TER and claudin-2 levels, FD4 permeability and ZO-1 localization were fully recovered. The IFN-γ-induced FD4 permeability in primary human colonoids was fully rescued by tofacitinib.
conclusionsThese data suggest differential therapeutic efficacy of tofacitinib in the rescue of pore vs leak-tight junction barrier defects and indicate a potential contribution of improved epithelial barrier function to the beneficial effects of tofacitinib in IBD patients.
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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.