ReviewGut2020
Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells.
Review in Gut, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02749630 (An Observer-Blinded, Placebo-Controlled, Multiple-Ascending, Dose-Escalation Study to Explore the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeat Intravenous Administrations of UTTR1147A in Healthy Volunteers and Patients With Ulcerative Colitis and Crohn's Disease), which is not on this map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
An Observer-Blinded, Placebo-Controlled, Multiple-Ascending, Dose-Escalation Study to Explore the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeat Intravenous Administrations of UTTR1147A in Healthy Volunteers and Patients With Ulcerative Colitis and Crohn's Disease
Who cites it
82 citing papers in PubMed, 150 citations in OpenAlex.
- Trial
- Failed Mucosal Allostasis Distinguishes Murine IgG- From IgE-Mediated Recurrent Severe Anaphylaxis.Allergy · 2026Article
- Urolithin A activates aryl hydrocarbon receptor-NLRP6-mediated pathways in intestinal epithelial cells to modulate mucosal immunity and strengthen gut barrier integrity.Nature communications · 2026Article
- Review
- The gut as a central hub for multi-organ crosstalk in aging.Cellular and molecular life sciences : CMLS · 2026Review
- Gut microbiota-derived tryptophan metabolite indole-3-carboxaldehyde enhances intestinal barrier function via aryl hydrocarbon receptor/AMP-activated protein kinase signaling activation.Animal bioscience · 2026Article
- MAIT Cells Maintain Intestinal Homeostasis Through IL-22 in an Experimental Colitis.Journal of inflammation research · 2026Article
- Gut microbiota-derived metabolites and IL-22 signaling in inflammatory bowel disease: context-dependent regulation of mucosal repair and inflammation.Frontiers in immunology · 2026Review
- Rehydration rescues Il22Nature communications · 2025Article
- Ustekinumab enhances intestinal stenosis resolution by modulating fibrotic pathways in crohn's disease: a retrospective single-center study with translational analysis.BMC gastroenterology · 2025Article
- Intestinal Epithelial-Derived USP13 Alleviates Colonic Inflammation by Suppressing GRP78-mediated Endoplasmic Reticulum Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Plasma interleukin-22 concentration and disease activity in inflammatory bowel disease.Scientific reports · 2025Observational
- The reciprocal regulation between autophagy and IL-22: implications for immunity and therapy.Clinical and experimental medicine · 2025Review
- Review
- Microbial remodeling of gut tryptophan metabolism and indole-3-lactate production regulate epithelial barrier repair and viral suppression in human and simian immunodeficiency virus infections.Mucosal immunology · 2025Article
- The Role of Interleukin-24 and Downstream Pathways in Inflammatory and Autoimmune Diseases.Cell biochemistry and biophysics · 2025Review
- Targeting the IL-23 Receptor Gene: A Promising Approach in Inflammatory Bowel Disease Treatment.International journal of molecular sciences · 2025Review
- The Intestinal Macrophage-Intestinal Stem Cell Axis in Inflammatory Bowel Diseases: From Pathogenesis to Therapy.International journal of molecular sciences · 2025Review
- Novel treatment of acute and acute-on-chronic liver failure: Interleukin-22.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 5 countries.
Funding
Abstract
objectiveThe functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22-mediated regulation of colonic epithelial cells.
designTo investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells, we employed a three-dimentional mini-gut epithelial organoid system, in vivo disease models and transcriptomic datasets in human IBD.
resultsAs well as inducing transcriptional modules implicated in antimicrobial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional programme in colonic epithelial cells. In the colon of patients with active colonic Crohn's disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response.
conclusionsOur data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22-regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis. TRIAL REGISTRATION NUMBER: NCT02749630.
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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.