ArticleNature immunology2025
The IL-22-oncostatin M axis promotes intestinal inflammation and tumorigenesis.
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Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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25citing papers in PubMed, 2 pooled it
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- IBD-related inflammatory memory and colorectal cancer: epigenetic mechanisms and microbiome interventions.Frontiers in immunology · 2026Pooled it
- Large-scale multi-trait genome-wide analysis for inflammatory bowel disease reveals new insights into its molecular mechanisms and emphasizes the roles of systemic immune regulation.Briefings in bioinformatics · 2025Pooled it
- The gut microbiota as a regulator of intestinal stem-cell fate: bacterial and fungal control of differentiation and regeneration.Gut microbes · 2026Review
- BRD4 contributes to the cytokine-induced acquisition of an IL-13RA2-positive inflammatory fibroblast phenotype.Journal of Crohn's & colitis · 2026Article
- Galangin ameliorates Salmonella Pullorum-induced enteritis in Danzhou chicks through gut microbiota-derived indole-3-lactic acid-mediated AHR activation.Poultry science · 2026Article
- USP9X trims STAT1 to curb oncostatin M activity and intestinal inflammation.Cellular & molecular immunology · 2026Article
- Macrophage USP9X attenuates colitis by restricting oncostatin M production via K27-linked deubiquitination of STAT1.Cellular & molecular immunology · 2026Article
- Fungi and colorectal cancer: from dysregulation to clinical translation.Gut pathogens · 2026Review
- Review
- Injectable pH-responsive carboxymethyl cellulose hydrogel for sustained delivery of IL-22 in the treatment of alcoholic liver disease.Journal of nanobiotechnology · 2026Article
- Cytokine and chemokine networks in colorectal cancer.Frontiers in immunology · 2026Review
- Fibroblasts selectively modulate immune cell-derived cytokine effects on tumor cells in colorectal cancer.Frontiers in immunology · 2026Article
- Decoding innate lymphoid cell heterogeneity and plasticity in colorectal cancer.Clinical and translational medicine · 2026Article
- Inflammatory and Immune Pathways Driving Tumor Necrosis Factor Inhibitor Resistance in Ulcerative Colitis.Journal of inflammation research · 2026Review
- Microbiota-miR-101 interactions in obesity-associated colorectal cancer: from barrier dysfunction to precision therapeutic strategies.Frontiers in pharmacology · 2026Review
- Epigenetic Inflammation Supports Tumorigenesis: Activator Protein 1 Drives Stem Cell Memory to Augment Colitis and Cancer.Research (Washington, D.C.) · 2026Article
- Article
- Intestinal stem and progenitor cells exhibit distinct adaptive responses to inflammatory stress in IBD.Stem cell research & therapy · 2025Article
- IL-1β-induced STAT3 activation drives IL-17-producing CD8Journal of translational medicine · 2025Article
- Human Microbiome as an Immunoregulatory Axis: Mechanisms, Dysbiosis, and Therapeutic Modulation.Microorganisms · 2025Review
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Authors and funding
38 authors.
Roodline Cineus *Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-4393-5757
Yanjiang Luo *Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0009-0003-0401-467X
Mariia SaliutinaDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Subhakankha MannaDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-2360-0618
Camila A CancinoDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Luis Velasco BlázquezDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Lifen WangDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Diana BöselDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Aya AbdelrahmanDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Joanna E KlementowiczDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Alexis ScherlDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Saskia HainbuchDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Béatrice BréartDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Gino KwonDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Agata KonopkaDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Gabriela M GuerraGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.
Elena von CoburgDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0009-0001-8546-8854
Lorenz GerbethDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Juliette RoelsDepartment of Computational Sciences, Genentech, South San Francisco, CA, USA.
Frederik HeinrichGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.ORCID http://orcid.org/0000-0001-6097-5422
Nils MüllerGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.ORCID http://orcid.org/0000-0003-1559-7711
Pawel DurekGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.ORCID http://orcid.org/0000-0002-6179-0670
Nikolaus DeigendeschInstitute of Innate Immunity, Department for Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-6036-3327
James ZiaiDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Jeffrey HungDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Thomas ConradGenomics Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.ORCID http://orcid.org/0000-0001-5618-6295
TRR241 IBDome Consortium
Anja A KühliPATH.Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-2293-5387
Stefan WirtzDepartment of Medicine 1, Friedrich-Alexander University, Erlangen, Germany.ORCID http://orcid.org/0000-0001-6936-7431
Max LöhningDepartment of Rheumatology and Clinical Immunology, Experimental Immunology and Osteoarthritis Research, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0001-6382-7281
Mary KeirDepartment of Immunology Discovery, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0637-4092
Andreas DiefenbachGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.ORCID http://orcid.org/0000-0002-9176-9530
Mir-Farzin MashreghiGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.ORCID http://orcid.org/0000-0002-8015-6907
Britta SiegmundDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-0055-958X
Michael SchumannDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Chiara RomagnaniGerman Rheumatology Research Center (DRFZ), Leibniz Institute, Berlin, Germany.ORCID http://orcid.org/0000-0002-5167-7463
Nathaniel R WestDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Ahmed N HegazyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ahmed.hegazy@charite.de.ORCID http://orcid.org/0000-0002-2946-8251
Funding
Deutsche Forschungsgemeinschaft (German Research Foundation) TRR 241-A01 (375876048); SFB 1444/P11 (427826188); SPP 1937-DI764/9-2Deutsche Forschungsgemeinschaft (German Research Foundation) TRR 241-C03 (375876048); GRK 2318-B02 (318905415)Deutsche Forschungsgemeinschaft (German Research Foundation) TRR 241-C03 B02 (375876048); RO 3565/7-1EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 101078069EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) LCAdapt (101055309); GlycanTrigger (101093997)EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) MEM-CLONK (101055157)Volkswagen Foundation (VolkswagenStiftung) 92087
Abstract
Multicellular cytokine networks drive intestinal inflammation and colitis-associated cancer (CAC). Interleukin-22 (IL-22) exerts both protective and pathogenic effects in the intestine, but the mechanisms that regulate this balance remain unclear. Here, we identify that IL-22 directly induces responsiveness to the IL-6 family cytokine oncostatin M (OSM) in intestinal epithelial cells (IECs) by activating STAT3 and upregulating the OSM receptor. In turn, OSM synergizes with IL-22 to sustain STAT3 activation in IECs and promote proinflammatory epithelial adaptation and immune cell chemotaxis to the inflamed intestine. Conditional deletion of the OSM receptor in IECs protects mice from both colitis and CAC, and pharmacological blockade of OSM attenuates established CAC. Thus, IL-22 and OSM form a pathogenic circuit that drives inflammation and tumorigenesis. Our findings reveal a previously unknown mechanism by which OSM supports intestinal pathology and highlight the IL-22-OSM axis as a promising therapeutic target for inflammatory bowel disease and CAC.
Indexed as
CarcinogenesisColitisColitis-Associated NeoplasmsInterleukinsOncostatin MAnimalsEpithelial CellsHumansInflammationInterleukin-22Intestinal MucosaMiceMice, Inbred C57BLMice, KnockoutReceptors, Oncostatin MSignal TransductionInterleukin-22InterleukinsOncostatin MReceptors, Oncostatin MStat3 protein, mouseSTAT3 Transcription Factor
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