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NOVEL APPROACHES TO PATHOGENESIS, DIAGNOSIS AND TREATMENT OF AUTOIMMUNE DISEASES BASED ON NEW INSIGHTS INTO THYMUS-DEPENDENT SELF-TOLERANCE

Objective

Autoimmune diseases are a significant burden for the quality of life and health care cost. Despite intense research efforts, the mechanisms underlying the development of autoimmune diseases are still largely obscure. This obvious ignorance explains why the current treatment of these chronic diseases remains inadequate and is associated with severe side effects. Here we propose an original and new approach to tackle this problem.Our approach is mainly based on the major biological function of the thymus, i.e. to ensure the generation of a diverse repertoire of T cell receptors that are self-tolerant.The thymus achieves this goal by using two complementary mechanisms: a) apoptotic deletion and developmental arrest of T cells bearing a receptor (TCR) with high affinity for self-antigens presented by major histocompatibility complex (MHC) proteins expressed by thymic epithelial and dendritic cells, and b) generation of self-antigen specific regulatory T cells. The escape from central self-tolerance now appears to play a prominent role in the development of autoimmune diseases.

Six workpackages will achieve the objectives of this proposal:
1. Intrathymic promiscuous gene expression and self-peptide tolerogenic therapy.
2. Preclinical studies of the autoimmune regulator (AIRE) in gene therapy.
3. Interest of anti-Coxsackievirus B4 vaccination for prevention of type 1 diabetes.
4. Exploration of a new T cell pathway governing autoimmunity and allergy.
5. Development, function and therapeutic utility of regulatory T cells in autoimmune diseases and asthma.
6. Evaluation of thymic epithelial stem cell therapeutic potential.

This ambitious research project will lead to new insights into disease mechanisms, and will concurrently provide a unique platform for innovative diagnostics and for disease-specific therapy aimed at a cure and prevention of autoimmune diseases, such as type 1 diabetes as a prototypic target of this proposal.

Call for proposal

FP6-2002-LIFESCIHEALTH
See other projects for this call

Funding Scheme

IP - Integrated Project

Coordinator

UNIVERSITY OF LIEGE
Address
Place Du Vingt-août 7
Liege
Belgium

Participants (26)

APEIRON BIOLOGICS
Austria
Address
Dr. Ignaz Seipel- Platz 2
Vienna
BAYERISCHE JULIUS MAXIMILIANS-UNIVERSITAET WUERZBURG
Germany
Address
Sanderring 2
Wuerzburg
CENTRE HOSPITALIER REGIONAL ET UNIVERSITAIRE DE LILLE
France
Address
Avenue Oscar Lambret 2
Lille
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Chemin Joseph Aiguier 31
Marseille
CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
University Offices, Wellington Square
Oxford
DEPARTMENT OF EXPERIMENTAL MEDECINE AND PATHOLOGY - UNIVERSITY LA SAPIENZA
Italy
Address
Viale Regina Elena 324
Roma
DEUTSCHES KREBSFORSCHUNGSZENTRUM (GERMAN CANCER RESEARCH CENTER)
Germany
Address
Im Neuenheim Feld 280
Heidelberg
FIT BIOTECH OYJ PLC
Finland
Address
Biokatu 10
Tampere
IMBA - INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Austria
Address
Dr.-bohr-gasse 3
Vienna
INGENIUM PHARMACEUTICALS GMBH
Germany
Address
Fraunhoferstraße 13
Martinsried
INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE
France
Address
Rue De Tolbiac, 101
Paris
INSTITUTE OF MEDICAL AND VETERINARY SCIENCE
Australia
Address
14 Rundle Mall
Adelaide
INSTITUTE OF MOLECULAR BIOTECHNOLOGY OF THE AUSTRIA ACADEMY OF SCIENCES
Austria
Address
Dr. Ignaz Seipel-platz 2
Vienna
KING'S COLLEGE LONDON'
United Kingdom
Address
Strand
London
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany
Address
Geschwister-scholl-platz 1
Muenchen
MAX-PLANCK-SOCIETY FOR THE ADVANCEMENT OF SCIENCE, MAX-PLANCK-INSTITUTE OF IMMUNOBIOLOGY
Germany
Address
Stuebeweg 51
Freiburg
PROIMMUNE LTD
United Kingdom
Address
Magdalen Center, Oxford Science Park
Oxford
RESEARCH INSTITUTE OF MOLECULAR PATHOLOGY
Austria
Address
Dr. Bohr-gasse 7
Vienna
RUPRECHT-KARLS-UNIVERSITÄT HEIDELBERG
Germany
Address
Seminarstrasse 2
Heidelberg
THE WALTER AND ELIZA HALL INSTITUTE FOR MEDICAL RESEARCH
Australia
Address
Royal Parade 1G
Parkville, Victoria
UNIVERSITAT AUTONOMA DE BARCELONA
Spain
Address
Campus Universitat Autònoma De Barcelona
Bellaterra (Cerdanyola Del Valles
UNIVERSITE DE MONTREAL
Canada
Address
Boulevard Edouard Montpetit 2900
Montreal
UNIVERSITY OF BASEL
Switzerland
Address
Petersgraben 35
Basel
UNIVERSITY OF BIRMINGHAM
United Kingdom
Address
Edgbaston
Birmingham
UNIVERSITY OF TARTU
Estonia
Address
Ülikooli Str. 18
Tartu
ZENTECH
Belgium
Address
Avenue Pré-aily 10
Angleur