ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Effects of Lactobacillus reuteri LR1 on the growth performance, intestinal morphology, and intestinal barrier function in weaned pigs.Journal of animal science · 2018Trial
- Shared Genetics in Celiac Disease and Inflammatory Bowel Disease Specify a Greater Role for Intestinal Epithelial Cells.International journal of molecular sciences · 2025Review
- TYK2 Protein Expression and Its Potential as a Tissue-Based Biomarker for the Diagnosis of Colorectal Cancer.Cancers · 2024Article
- Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway.Acta cirurgica brasileira · 2023Article
- Epithelial dysfunction is prevented by IL-22 treatment in a Citrobacter rodentium-induced colitis model that shares similarities with inflammatory bowel disease.Mucosal immunology · 2022Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Tyk2 is a tumor suppressor in colorectal cancer.Oncoimmunology · 2022Article
- Cranberry polyphenols and agave agavins impact gut immune response and microbiota composition while improving gut barrier function, inflammation, and glucose metabolism in mice fed an obesogenic diet.Frontiers in immunology · 2022Article
- Differential colitis susceptibility of Th1- and Th2-biased mice: A multi-omics approach.PloS one · 2022Article
- Jakinibs of All Trades: Inhibiting Cytokine Signaling in Immune-Mediated Pathologies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A Decade of JAK Inhibitors: What Have We Learned and What May Be the Future?Arthritis & rheumatology (Hoboken, N.J.) · 2021Review
- Tyrosine Kinase 2 Signalling Drives Pathogenic T cells in Colitis.Journal of Crohn's & colitis · 2021Article
- Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis.Nature reviews. Rheumatology · 2020Review
- TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.The Journal of clinical investigation · 2020Article
- TYK2 in Tumor Immunosurveillance.Cancers · 2020Review
- The role of IL22 polymorphisms on liver cirrhosis in patients with hepatitis B virus: A case control study.Medicine · 2019Article
- Review
- Janus kinases to jakinibs: from basic insights to clinical practice.Rheumatology (Oxford, England) · 2019Review
- Interleukin 22 Expands Transit-Amplifying Cells While Depleting Lgr5Cellular and molecular gastroenterology and hepatology · 2019Article
- Deficiency in STAT1 Signaling Predisposes Gut Inflammation and Prompts Colorectal Cancer Development.Cancers · 2018Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22-STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice. Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3.
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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.