ArticleInternational journal of molecular sciences2022
T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Targeted analysis of sphingolipids and cytokines in plasma of dairy cows after calving reveals distinct impacts of systemic inflammation, ketosis, and mastitis.Journal of animal science and biotechnology · 2026Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Elevated long-to-very-long-chain ceramide ratio correlates with disease severity in inflammatory bowel disease and primary sclerosing cholangitis.Scientific reports · 2025Article
- Identification of prognostic and therapeutic biomarkers associated with macrophage and lipid metabolism in pancreatic cancer.Scientific reports · 2025Article
- How ceramides affect the development of colon cancer: from normal colon to carcinoma.Pflugers Archiv : European journal of physiology · 2024Review
- Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity.Communications biology · 2024Article
- Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response.Cell reports · 2024Article
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
- Review
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota.Frontiers in immunology · 2023Review
- Associations between genetic variants in sphingolipid metabolism pathway genes and hepatitis B virus-related hepatocellular carcinoma survival.Frontiers in oncology · 2023Article
- Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice.Oxidative medicine and cellular longevity · 2022Article
- How sphingolipids affect T cells in the resolution of inflammation.Frontiers in pharmacology · 2022Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
To better understand the role of sphingolipids in the multifactorial process of inflammatory bowel disease (IBD), we elucidated the role of CerS4 in colitis and colitis-associated cancer (CAC). For this, we utilized the azoxymethane/dextran sodium sulphate (AOM/DSS)-induced colitis model in global CerS4 knockout (CerS4 KO), intestinal epithelial (CerS4 Vil/Cre), or T-cell restricted knockout (CerS4 LCK/Cre) mice. CerS4 KO mice were highly sensitive to the toxic effect of AOM/DSS, leading to a high mortality rate. CerS4 Vil/Cre mice had smaller tumors than WT mice. In contrast, CerS4 LCK/Cre mice frequently suffered from pancolitis and developed more colon tumors. In vitro, CerS4-depleted CD8+ T-cells isolated from the thymi of CerS4 LCK/Cre mice showed impaired proliferation and prolonged cytokine production after stimulation in comparison with T-cells from WT mice. Depletion of CerS4 in human Jurkat T-cells led to a constitutively activated T-cell receptor and NF-κB signaling pathway. In conclusion, the deficiency of CerS4 in T-cells led to an enduring active status of these cells and prevents the resolution of inflammation, leading to a higher tumor burden in the CAC mouse model. In contrast, CerS4 deficiency in epithelial cells resulted in smaller colon tumors and seemed to be beneficial. The higher tumor incidence in CerS4 LCK/Cre mice and the toxic effect of AOM/DSS in CerS4 KO mice exhibited the importance of CerS4 in other tissues and revealed the complexity of general targeting CerS4.
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Registered trials
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