El-Hindi, Khadija, Brachtendorf, Sebastian, Hartel, Jennifer Christina, Oertel, Stephanie, Birod, Kerstin, Merz, Nadine, Trautmann, Sandra, Thomas, Dominique ORCID: 0000-0002-4153-3669, Weigert, Andreas ORCID: 0000-0002-7529-1952, Schaeufele, Tim J., Scholich, Klaus, Schiffmann, Susanne ORCID: 0000-0001-5035-2504, Ulshoefer, Thomas, Utermoehlen, Olaf and Groesch, Sabine ORCID: 0000-0002-7262-6307 (2022). T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model. Int. J. Mol. Sci., 23 (3). BASEL: MDPI. ISSN 1422-0067

Full text not available from this repository.

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-kappa B 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
El-Hindi, KhadijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brachtendorf, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartel, Jennifer ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oertel, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Birod, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merz, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trautmann, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, DominiqueUNSPECIFIEDorcid.org/0000-0002-4153-3669UNSPECIFIED
Weigert, AndreasUNSPECIFIEDorcid.org/0000-0002-7529-1952UNSPECIFIED
Schaeufele, Tim J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholich, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiffmann, SusanneUNSPECIFIEDorcid.org/0000-0001-5035-2504UNSPECIFIED
Ulshoefer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utermoehlen, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Groesch, SabineUNSPECIFIEDorcid.org/0000-0002-7262-6307UNSPECIFIED
URN: urn:nbn:de:hbz:38-669376
DOI: 10.3390/ijms23031866
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 23
Number: 3
Date: 2022
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COLORECTAL NEOPLASIA; ULCERATIVE-COLITIS; CANCER; MICE; SMAD7; SPHINGOLIPIDS; AZOXYMETHANE; METABOLISM; RISK; CARCINOGENESISMultiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66937

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item