ArticleNature2015
Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 686 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.
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Who cites it
686 citing papers in PubMed, 1,086 citations in OpenAlex.
- Intestinal Stem Cells: Regulation, Plasticity, and Therapeutic Potential.Methods in molecular biology (Clifton, N.J.) · 2027Review
- The gut microbiota as a regulator of intestinal stem-cell fate: bacterial and fungal control of differentiation and regeneration.Gut microbes · 2026Review
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- Sonogenetic Control of Engineered Probiotics for the Treatment of MASH by Modulating the Gut-Liver Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microbiome-Derived Tryptophan Metabolites Regulate AhR Signaling to Restore Epithelial Barrier Integrity in Inflammatory Bowel Disease.MicrobiologyOpen · 2026Review
- Failed Mucosal Allostasis Distinguishes Murine IgG- From IgE-Mediated Recurrent Severe Anaphylaxis.Allergy · 2026Article
- Immunomodulatory Function of Soluble Dietary Fiber: Toward Application for Prevention and Treatment of Food Allergies.Current allergy and asthma reports · 2026Review
- Long Noncoding RNANon-coding RNA · 2026Article
- IL-22 increases proglucagon-expressing enteroendocrine cells via STAT3 in human iPSC-derived intestinal epithelium.Endocrinology · 2026Article
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Engineered outer membrane vesicle-like nanoparticles from Lactobacillus plantarum for oral IL-22 mRNA delivery and treatment of DSS-induced colitis.Molecular and cellular biochemistry · 2026Article
- Concerted changes in the pediatric single-cell intestinal ecosystem before and after anti-TNF blockade.eLife · 2026Article
- Intestinal epithelial memory: from inflammatory imprinting to metabolite-shaped immune tolerance.Barrier immunity · 2026Article
- γδ T cells in colorectal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Fecal microbiota transplantation in the treatment of acute graft-versus-host disease: A retrospective study performed by the Complications Working Party and Pediatric Diseases Working Party of the EBMT.Bone marrow transplantation · 2026Article
- Intestinal Epithelial MHC-II at the Interface of Microbiota, Immunity, and Inflammation.International journal of molecular sciences · 2026Review
- Balancing act of cytokines in controlling the severity ofInfection and immunity · 2026Review
- Rhoifolin Alleviates Ulcerative Colitis by Targeting NMNAT1 and Activating SIRT1-FOXO1 Signaling to Enhance ILC3s Effector Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
626 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 3 countries.
Funding
Abstract
Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5(+) crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innate lymphoid cells (ILCs), potent producers of interleukin-22 (IL-22) after intestinal injury, increase the growth of mouse small intestine organoids in an IL-22-dependent fashion. Recombinant IL-22 directly targeted ISCs, augmenting the growth of both mouse and human intestinal organoids, increasing proliferation and promoting ISC expansion. IL-22 induced STAT3 phosphorylation in Lgr5(+) ISCs, and STAT3 was crucial for both organoid formation and IL-22-mediated regeneration. Treatment with IL-22 in vivo after mouse allogeneic bone marrow transplantation enhanced the recovery of ISCs, increased epithelial regeneration and reduced intestinal pathology and mortality from graft-versus-host disease. ATOH1-deficient organoid culture demonstrated that IL-22 induced epithelial regeneration independently of the Paneth cell niche. Our findings reveal a fundamental mechanism by which the immune system is able to support the intestinal epithelium, activating ISCs to promote regeneration.
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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.