Objective APECED patients suffer from tissue-specific destructive autoimmunity, affecting principally endocrine organs. They indicate a profound defect in immune maturation, especially in the mechanisms leading to tolerance against self-antigens, which occur during negative selection in the thymus. AIRE, the mutated gene in APECED and necessary for maintenance of T-cell tolerance, is responsible for intrathymic expression of peripheral autoantigens. Indeed, AIRE has an activity of transcriptional regulator. However the exact mechanism how AIRE influences the transcription of autoantigens remains elusive. The knowledge about AIRE functional targets and partners will have a significant input to the understanding of AIRE in these processes and immune tolerance in general.Recently Hamish's group has discovered a new protein involved in epigenetic processes, which they are calling AIP (AIRE interacting protein). Only few things are known on this new and exiting molecule. Its expression and sub-cellular localization mirrors A IRE in the thymus in vivo and it also interact with AIRE in vitro. We purpose to analyse the role of AIP by multidisciplinary approach (genetic and immunology). Using uniqueness resources such as transgenics and KO technologies, we will study the general autoimmune phenomena in AIP KO mice. Then we will investigate the role of AIP in control of thymic selection and also the role of AIP in control of peripheral tolerance by cross presentation of self-antigens. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesclinical medicineallergologymedical and health sciencesclinical medicinetransplantation Keywords AIRE thymus tolerance Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.2 - Marie Curie Outgoing International Fellowships (OIF) Call for proposal FP6-2005-MOBILITY-6 See other projects for this call Funding Scheme OIF - Marie Curie actions-Outgoing International Fellowships Coordinator INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE Address Institut francois magendie 146 rue leo saignat Bordeaux France See on map Links Website Opens in new window EU contribution € 0,00 Participants (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH Australia EU contribution € 0,00 Address 1g royal paradeparkville victoria Melbourne See on map Links Website Opens in new window