Toll-Interacting Protein Regulates Immune Cell Infiltration and Promotes Colitis-Associated Cancer
Christina Begka,
Céline Pattaroni,
Catherine Mooser,
Stéphane Nancey,
Kathy D. McCoy,
Dominique Velin,
Michel H. Maillard
Affiliations
Christina Begka
Service of Gastroenterology and Hepatology, Department of Medicine, University Hospital of Lausanne, CHUV-Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland; University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
Céline Pattaroni
Service of Pneumology, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Chemin de Boveresses 155, 1066 Epalinges, Switzerland
Catherine Mooser
Maurice Müller Laboratories (DBMR), Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland
Stéphane Nancey
Lyon Sud Hospital, Hospices Civils de Lyon, CHU, Lyon, France
Kathy D. McCoy
Maurice Müller Laboratories (DBMR), Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
Dominique Velin
Service of Gastroenterology and Hepatology, Department of Medicine, University Hospital of Lausanne, CHUV-Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland; University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
Michel H. Maillard
Service of Gastroenterology and Hepatology, Department of Medicine, University Hospital of Lausanne, CHUV-Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland; University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland; Crohn and Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland; Corresponding author
Summary: 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. : Biological Sciences; Immunology; Cancer Subject Areas: Biological Sciences, Immunology, Cancer
