Objectif Lipids play crucial roles in metabolism, immunity and cancer. In addition to their function as inflammatory mediators, lipids serve as antigens presented by CD1d and activate a subset of T cells called natural killer T (NKT) cells. While NKT cells are critical for human immunity, their uncontrolled activation contributes to inflammatory bowel disease (IBD), a group of diseases characterized by chronic intestinal inflammation and an increased risk of colorectal cancer (CRC). Specifically, NKT cells are the major source of pathogenic TH2 cytokines in the inflammatory bowel disease ulcerative colitis (UC), are sufficient to cause intestinal inflammation in mice, and are required for colitis and colitis-associated cancer in a mouse model of UC. These observations suggest that targeting of lipid antigen presentation may be of therapeutic value in IBD, where current therapies are of limited efficacy and aim at control rather than cure of disease.Here, I propose to identify the lipid antigens responsible for NKT cell-mediated intestinal inflammation and colitis-associated cancer in human IBD and mouse models of intestinal inflammation and to develop therapeutic strategies for interference with pathogenic lipid antigen presentation. Specifically, I propose to characterize the intestinal inflammation- and cancer-associated CD1d lipidome based on novel in vitro and in vivo models of cleavable CD1d and a recently established lipidomics approach. Furthermore, I propose to develop strategies for inhibition of the generation, loading and presentation of inflammation- and cancer-associated lipid antigens. These studies combine biochemical, immunological and high-throughput technologies in an interdisciplinary manner to provide the knowledge required for the generation of novel, efficacious therapies for the treatment of IBD. These studies will have major implications for IBD and other inflammatory, infectious, and neoplastic diseases at mucosal barriers. Champ scientifique medical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasenatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicineoncologycolorectal cancer Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Appel à propositions ERC-2013-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil TECHNISCHE UNIVERSITAET DRESDEN Contribution de l’UE € 1 401 711,42 Adresse HELMHOLTZSTRASSE 10 01069 Dresden Allemagne Voir sur la carte Région Sachsen Dresden Dresden, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Chercheur principal Sebastian Zeißig (Dr.) Contact administratif Friederieke Noack (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire TECHNISCHE UNIVERSITAET DRESDEN Allemagne Contribution de l’UE € 1 401 711,42 Adresse HELMHOLTZSTRASSE 10 01069 Dresden Voir sur la carte Région Sachsen Dresden Dresden, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Chercheur principal Sebastian Zeißig (Dr.) Contact administratif Friederieke Noack (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL Participation terminée Allemagne Contribution de l’UE € 98 288,58 Adresse OLSHAUSENSTRASSE 40 24118 Kiel Voir sur la carte Région Schleswig-Holstein Schleswig-Holstein Kiel, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Contact administratif Linda Pialek (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée