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 therapy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunologyautoimmune diseases
- medical and health sciencesclinical medicineallergology
- medical and health sciencesclinical medicinetransplantation
Call for proposal
FP6-2005-MOBILITY-6
See other projects for this call
Funding Scheme
OIF - Marie Curie actions-Outgoing International FellowshipsCoordinator
BORDEAUX
France