Toll-Interacting Protein Regulates Immune Cell Infiltration and Promotes Colitis-Associated Cancer.

Begka, Christina; Pattaroni, Céline; Mooser, Catherine; Nancey, Stéphane; McCoy, Kathy D.; Velin, Dominique; Maillard, Michel H. (2020). Toll-Interacting Protein Regulates Immune Cell Infiltration and Promotes Colitis-Associated Cancer. iScience, 23(3), p. 100891. Elsevier 10.1016/j.isci.2020.100891

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Expression of Toll-interacting protein (Tollip), a potent TLR modulator, decreases in patients with inflammatory bowel diseases (IBD), whereas Tollip-/- mice are susceptible to colitis. Tollip expression was shown to be reduced in sporadic adenoma. In contrast, we found variable Tollip expression in patients with colitis-associated adenomas. In Tollip-/- mice challenged to develop colitis-associated cancer (CAC), tumor formation was significantly reduced owing to decreased mucosal proliferative and apoptotic indexes. This protection was associated with blunt inflammatory responses without significant changes in microbial composition. mRNA expression of Cd62l and Ccr5 homing receptors was reduced in colons of untreated Tollip-/- mice, whereas CD62L+ CD8+ T cells accumulated in the periphery. In Tollip-deficient adenomas Ctla-4 mRNA expression and tumor-infiltrating CD4+ Foxp3+ regulatory T cell (Treg) were decreased. Our data show that protection from CAC in Tollip-deficient mice is associated with defects in lymphocyte accumulation and composition in colitis-associated adenomas.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Mooser, Catherine and McCoy, Kathleen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2589-0042

Publisher:

Elsevier

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

22 Dec 2020 14:13

Last Modified:

22 Dec 2020 14:13

Publisher DOI:

10.1016/j.isci.2020.100891

PubMed ID:

32114379

Uncontrolled Keywords:

Biological Sciences Cancer Immunology

BORIS DOI:

10.7892/boris.149742

URI:

https://boris.unibe.ch/id/eprint/149742

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