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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.

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