ArticleThe Journal of clinical investigation2021
T cell protein tyrosine phosphatase protects intestinal barrier function by restricting epithelial tight junction remodeling.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- ABCG2 Upregulation Involving AKT/NF-κB Signaling Contributes to Intestinal Barrier Dysfunction in Inflammatory Bowel Disease.Digestive diseases and sciences · 2026Article
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- A Novel PTPN2 Isoform Differentially Regulates Immune Response.European journal of immunology · 2026Article
- Immunoregulatory protein-hybrid extracellular vesicles via self-loadable backbone cyclization for oral inflammatory bowel disease therapy.Bioactive materials · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Cyanidin-3,5-O-Glucoside Alleviates DSS-Induced Colon Barrier Dysfunction and Fibrosis Through Autophagy-Associated Pathway-Mediated Inflammation Repression in a C57BL/6J Mouse Model.Applied biochemistry and biotechnology · 2026Article
- Inflammatory bowel diseases: pathological mechanisms and therapeutic perspectives.Molecular biomedicine · 2026Review
- "Golden cicada-escape" style colon-targeted pellets for ulcerative colitis by balancing oxidative stress and repairing colonic barrier.Materials today. Bio · 2025Article
- Intestinal epithelial PTPN2 limits pathobiont colonization by immune-directed antimicrobial responses.Gut microbes · 2025Article
- TheGut microbes · 2025Article
- Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.Acta pharmaceutica Sinica. B · 2025Review
- Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.Journal of autoimmunity · 2025Article
- Article
- ModifiedWorld journal of gastroenterology · 2025Article
- Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways.Inflammatory bowel diseases · 2025Review
- Bile acids and gut microbiota: interactions and impacts on polycystic ovary syndrome.Frontiers in microbiomes · 2025Review
- The JAK inhibitor, Tofacitinib, Corrects the Overexpression of CEACAM6 and Limits Susceptibility to AIEC Caused by Reduced Activity of the IBD Associated Gene,medRxiv : the preprint server for health sciences · 2024Article
- Haploinsufficiency in PTPN2 leads to early-onset systemic autoimmunity from Evans syndrome to lupus.The Journal of experimental medicine · 2024Article
- Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms.Inflammatory bowel diseases · 2024Review
- Respiratory exposure to agricultural dust extract promotes increased intestinalAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies revealed that loss-of-function mutations in protein tyrosine phosphatase non-receptor type 2 (PTPN2) increase the risk of developing chronic immune diseases, such as inflammatory bowel disease (IBD) and celiac disease. These conditions are associated with increased intestinal permeability as an early etiological event. The aim of this study was to examine the consequences of deficient activity of the PTPN2 gene product, T cell protein tyrosine phosphatase (TCPTP), on intestinal barrier function and tight junction organization in vivo and in vitro. Here, we demonstrate that TCPTP protected against intestinal barrier dysfunction induced by the inflammatory cytokine IFN-γ by 2 mechanisms: it maintained localization of zonula occludens 1 and occludin at apical tight junctions and restricted both expression and insertion of the cation pore-forming transmembrane protein, claudin-2, at tight junctions through upregulation of the inhibitory cysteine protease, matriptase. We also confirmed that the loss-of-function PTPN2 rs1893217 SNP was associated with increased intestinal claudin-2 expression in patients with IBD. Moreover, elevated claudin-2 levels and paracellular electrolyte flux in TCPTP-deficient intestinal epithelial cells were normalized by recombinant matriptase. Our findings uncover distinct and critical roles for epithelial TCPTP in preserving intestinal barrier integrity, thereby proposing a mechanism by which PTPN2 mutations contribute to 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.