ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
IL-36γ and IL-36Ra Reciprocally Regulate Colon Inflammation and Tumorigenesis by Modulating the Cell-Matrix Adhesion Network and Wnt Signaling.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- LRMDA promotes intestinal mucosal barrier integrity and limits colitis and colon cancer.iScience · 2026Article
- IL-36 participated in airway remodeling in chronic asthma model by inducing epithelial-mesenchymal transition process.European journal of medical research · 2026Article
- Increased IL- 36γ in visceral adipose tissue as a key mediator of obesity-driven inflammation in colon cancer.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Circular RNA circPHLPP2 promotes tumor growth and anti-PD-1 resistance through binding ILF3 to regulate IL36γ transcription in colorectal cancer.Molecular cancer · 2024Article
- Wnt signaling pathway in spinal cord injury: from mechanisms to potential applications.Frontiers in molecular neuroscience · 2024Review
- PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity.Cell research · 2023Article
- Article
- New insights on IL‑36 in intestinal inflammation and colorectal cancer (Review).Experimental and therapeutic medicine · 2023Review
- Transcriptomic and functional analyses reveal a tumour-promoting role for the IL-36 receptor in colon cancer and crosstalk between IL-36 signalling and the IL-17/ IL-23 axis.British journal of cancer · 2023Article
- Review
- Regulation of Interleukin-36γ/IL-36R Signaling Axis by PIN1 in Epithelial Cell Transformation and Breast Tumorigenesis.Cancers · 2022Article
- IL-36γ and IL-36Ra Reciprocally Regulate Colon Inflammation and Tumorigenesis by Modulating the Cell-Matrix Adhesion Network and Wnt Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- IL-38 Gene Deletion Worsens Murine Colitis.Frontiers in immunology · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammatory bowel disease and colorectal cancer are associated with dysregulation of cytokine networks. However, it is challenging to target cytokines for effective intervention because of the overlapping functions and unpredictable interactions of cytokines in such diverse networks. Here, it is shown that IL-36γ and IL-36Ra, an agonist and an antagonist for IL-36R signaling respectively, reciprocally regulate the experimental colitis and the colon cancer development in mice. Knockout or neutralization of IL-36γ alleviates dextran sulfate sodium (DSS)-induced colitis and inhibits colon cancer development, whereas knockout of IL-36Ra exacerbates DSS-induced colitis and promotes colonic tumorigenesis in multiple colon cancer models in mice. Mechanistically, IL-36γ upregulates extracellular matrix and cell-matrix adhesion molecules and facilitates Wnt signaling, which is mitigated by IL-36Ra or IL-36γ neutralizing antibody. Consistently, IL-36γ levels are positively correlated with extracellular matrix levels and β-catenin levels in human colorectal tumor biopsies. These findings suggest the critical role of IL-36γ and IL-36Ra in gut inflammation and tumorigenesis and indicate that targeting the IL-36γ/IL-36Ra signal balance provides potential therapeutic strategy for inflammatory bowel disease and gastrointestinal cancers.
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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.