Clearance of apoptotic cells: discovery of autoantigens and therapy for autoimmune diseases

Objective

The clearance of dying cells is the last phase of apoptosis in vivo. Corpse removal prevents inflammation and autoimmunity. We plan to develop therapeutic strategies aimed to restore in vivo clearance, in order to prevent tissue damage and chronic inflammation. To this aim we will characterise the molecular machinery involved, using complementary approaches (from genetic screening in C. elegans to function complementation in autoimmune patient phagocytes). We will establish a panel of clearance defective animals bearing combined modifications of relevant genes and study the consequences of accumulation of apoptotic cells in selected tissues on the homeostasis of the organism. We will characterise the effect of molecular interventions in vivo in models of acute and chronic tissue inflammation. Finally we will exploit this system to identify novel autoantigens in vivo, which will be validated as diagnostic tools in patients with systemic autoimmune diseases.

Programme(s)

• FP5-LIFE QUALITY - Specific Programme for research, technological development and demonstration on "Quality of life and management of living resources", 1998-2002

Topic(s)

• 1.1.1.-3. - Key action The "Cell factory"

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR - ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO

Address

Via Olgettina 58
20132 Milano
Italy

Participants (8)

DIESSE DIAGNOSTICA SENESE SPA

Italy

Address

Via S. Vittore 36/1
20100 Milano

GENERA SPA

Italy

Address

Via Olgettina 58
20132 Milano

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

Address

Parc Scientifique De Luminy
13288 Marseille

INSTITUTE FOR INFECTIOUS DISEASES "LAZZARO SPALLANZANI"

Italy

Address

Via Portuense, 292
00149 Roma

UNIVERSITY OF DEBRECEN

Hungary

Address

Egyetem Tér. 1
Debrecen

UNIVERSITY OF ERLANGEN-NUREMBERG

Germany

Address

Egerlandstrasse 1
91058 Erlangen

UNIVERSITY OF ZURICH

Switzerland

Address

71,Raemistrasse 71
CH-8091 Zurich

University of Edinburgh

United Kingdom

Address

Old College South Bridge
EH1 1HN Edinburgh