OXYSTEROLS AND TR1

Oxysterols and IL-27-induced Type 1 regulatory T cells in Experimental Autoimmune Encephalomyelitis

Coordinatore	UNIVERSITE DE GENEVE    more  Organization address address: Rue du General Dufour 24 city: GENEVE postcode: 1211 contact info Titolo: Dr. Nome: Patrice Cognome: Lalive Email: send email Telefono: +41 22 372 83 18 Fax: +41 22 372 83 32
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	75˙000 €
EC contributo	75˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-CIG
Funding Scheme	MC-CIG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-09-01   -   2014-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITE DE GENEVE  Organization address address: Rue du General Dufour 24 city: GENEVE postcode: 1211 contact info Titolo: Dr. Nome: Patrice Cognome: Lalive Email: send email Telefono: +41 22 372 83 18 Fax: +41 22 372 83 32	CH (GENEVE)	coordinator	75˙000.00

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 Obiettivo del progetto (Objective)

'Accumulating evidence indicates that cholesterol metabolism plays a major role during acquired immune response. Cholesterol metabolites oxysterols have recently been proposed to be involved in the pathogenesis of multiple sclerosis (MS), considered to be the first cause of neurologic disability among young adults in occidental countries. MS is characterized by demyelination throughout the central nervous system associated with inflammatory infiltrates of lymphocytic and mononuclear cell. The balance between pathogenicity of effector T cells and negative regulation imposed by regulatory T cells plays a major role in its development. Two important classes of regulatory T cells within the CD4 subset are the Foxp3 T-cells (Tregs) and IL-10-producing type 1 regulatory T cells (Tr1). Interest in Tr1 cells was revived with the discovery that they could be differentiated with the cytokine IL-27. This provided impetus to evaluate the potential of IL-27-induced Tr1 cells in autoimmune diseases. Here we propose to study the role oxysterol during Tr1 cell differentiation. We recently performed a screening for different oxysterols converting enzymes during T cell differentiation and found that IL-27 specifically induced the membrane-associated enzyme CH25H. Based on these results, we first propose to study how modulation of CH25H and its product, 25-hydroxycholesterol, influences Tr1 cell biology in vitro and in vivo using the murine model of MS, experimental autoimmune encephalomyelitis. We further aim to dissect the molecular pathways by which oxysterols modulates Tr1 cells in order to define new putative pharmaceutical targets to enhance Tr1 cell number and function. Indeed, this project will help unravel the role of cholesterol metabolites during CD4 T cells differentiation and will assess their importance in the control of Tr1 cells during autoimmune diseases.'