Objectif Recent studies have shown dysregulation of microRNAs (miRNAs) in the mucosa of Crohn’s disease (CD) patients, suggesting a role for miRNAs as contributors to inflammatory bowel disease (IBD) susceptibility. The scientists from the host institution previously showed that ileal lesions in CD patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC), which are able to invade and to replicate within intestinal epithelial cells, and that functional autophagy is required to restrain AIEC replication. The overall hypothesis of this proposal is that miRNA pathway contributes to innate immune responses to AIEC colonization and/or inflammatory activities. The goal of our study is to determine the microRNAs dysregulated in host cells upon infection with AIEC, and the mechanism through which they contribute to responses of the host. In particular, three objectives will be addressed in this project: 1) To determine the potential role and mechanism by which miRNAs modulate the host responses of intestinal epithelial cells (IECs) to AIEC; 2) To investigate the regulation of CEACAM6, a host receptor for AIEC, by miRNAs in IECs during pathophysiological state, and in host responses to AIEC infection; and 3) To test the hypothesis that AIEC impair autophagy to replicate in host cells by modulating expression of host miRNAs. I propose to use IEC culture models of AIEC infection accompanied with bioinformatics tools to identify the miRNAs which are regulators of the key signaling pathways that modulate cross-talk between AIEC and host cells. The proposed studies in this project will shed light on the mechanism by which miRNAs are involved in host responses to AIEC infection, which could help to identify new biomarkers and potential therapeutic targets for IBD. Champ scientifique medical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasemedical and health sciencesbasic medicineimmunology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2011-IIF - Marie Curie Action: "International Incoming Fellowships" Appel à propositions FP7-PEOPLE-2011-IIF Voir d’autres projets de cet appel Régime de financement MC-IIF - International Incoming Fellowships (IIF) Coordinateur INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contribution de l’UE € 193 594,80 Adresse RUE DE TOLBIAC 101 75654 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Evelyne Bertino (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITE D'AUVERGNE CLERMONT-FERRAND 1 Participation terminée France Contribution de l’UE Aucune donnée Adresse BOULEVARD FRANCOIS MITTERAND 49 63001 Clermont-Ferrand Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Isabelle Rhit (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée