DENDRITIC CELLS

Identification and targeting of metabolic pathways in dendritic cells that regulate their immune polarizing function

Coordinatore	ACADEMISCH ZIEKENHUIS LEIDEN    more  Organization address address: Albinusdreef 2 city: LEIDEN postcode: 2333 ZA contact info Titolo: Mrs Nome: Linda Cognome: Ouwerkerk Email: send email Telefono: +31 71 5269596 Fax: +31 71 526 8275
Nazionalità Coordinatore	Netherlands [NL]
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-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2015
Periodo (anno-mese-giorno)	2015-01-01   -   2017-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	ACADEMISCH ZIEKENHUIS LEIDEN  Organization address address: Albinusdreef 2 city: LEIDEN postcode: 2333 ZA contact info Titolo: Mrs Nome: Linda Cognome: Ouwerkerk Email: send email Telefono: +31 71 5269596 Fax: +31 71 526 8275	NL (LEIDEN)	coordinator	75˙000.00

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 Obiettivo del progetto (Objective)

'Dendritic cells (DCs) are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cells (Th) and regulatory T cell responses (Treg). Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to changes in cellular metabolism. However, only recently, based on studies with T cells and macrophages, the picture is emerging that manipulation of cellular metabolism can be used to shape immune responses. This field of immunometabolism is rapidly evolving as one of the new frontiers in science. Nonetheless, little is known about the metabolic processes that support DC activation or about the metabolic requirements for DCs to drive Th1, Th2 or Treg responses. My proposal aims to fill this gap and focuses on the novel concept that cellular metabolism regulates the immune-polarizing properties of DCs.

Based on my recently published work and preliminary data, I hypothesize (1) that DCs priming Th1 responses are metabolically characterized by a switch to glycolytic metabolism, whereas Th2- or Treg-polarizing DCs, have a catabolic kind of metabolism that is dependent on mitochondrial fatty acid oxidation and oxidative phosphorylation and (2) that these states of metabolism are required for their immune-polarizing capacity.

To address this, my project aims (a) to characterize and compare the metabolic profiles of Th1-, Th2- and Treg-polarizing DCs and (b) to determine whether their metabolic programs underpin their T cell-polarizing capacity. (c) Based on these findings I aim to determine whether deliberate modulation of glycolytic or mitochondrial metabolism can alter the immune-polarizing capacity of DCs in such a way that they become either more immunogenic or tolerogenic in vivo. These studies can readily contribute to the development of novel metabolism-based strategies for improving DC-based immunotherapy.'