CD8DC FUNCTIONS

DNRG-1 as a marker to develop better models for characterising human and mouse dendritic subsets and for analysing their functional role in vivo

Coordinatore	CANCER RESEARCH UK    more  Organization address address: ST JOHN STREET 407 ANGEL BUILDING city: LONDON postcode: EC1V 4AD contact info Titolo: Ms. Nome: Holly Cognome: Elphinstone Email: send email Telefono: +44 2072693524 Fax: +44 207 269 3585
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	180˙783 €
EC contributo	180˙783 €
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-IEF-2008
Funding Scheme	MC-IEF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-10-01   -   2011-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CANCER RESEARCH UK  Organization address address: ST JOHN STREET 407 ANGEL BUILDING city: LONDON postcode: EC1V 4AD contact info Titolo: Ms. Nome: Holly Cognome: Elphinstone Email: send email Telefono: +44 2072693524 Fax: +44 207 269 3585	UK (LONDON)	coordinator	180˙783.75

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 Obiettivo del progetto (Objective)

'The dendritic cell (DC) system of antigen-presenting cells controls immunity and tolerance. The unresolved issues on DC heterogeneity represent an important hurdle in the development of DC-based immunotherapies. The identification of the DNGR-1 marker by the host lab allows us to develop better models for characterising human and mouse DC. In the mouse, this marker is selectively expressed in mouse CD8DC and then, we believe that it constitutes a better marker for CD8DC in vivo and, therefore, will carry out a detailed analysis of the distribution of DNGR-1 cells. We plan also to extend our work to imaging CD8DC and their interactions in vivo with T and B cells, and other DC as langerhans cells. This aim will be achieved by using and constructing knock-in (KI) mice that express a green or red fluorescent protein specifiquely to tag the CD8DC. The function of CD8DC remains speculative, in part because of the lack of models in which only one DC subtype could present a given antigen to T cells. We aim to circumvent this limitation by restricting the ability to present a given antigen to the CD8DC. They are also a lack of models in which DC subtypes can be selectively ablated. The host laboratory has constructed mice to deplete, transiently or constitutively the CD8DC. This model will allows us to assess the effect of ablation of CD8DC on the immune system. In humans, it has been argued that CD8DC are not present but this could simply reflect the fact that they have been overlooked. The host lab showed that DNGR-1 is also expressed by a small subset of human blood, sharing markers with mouse CD8DC. Then, we plan to characterise the functional properties of human DNGR-1DC in detail and determine whether they match those expected from the study of murine CD8DC. Based on our results, strategies that aim to define cancer immunotherapies could refine their approach, as our work will transpose mouse data to a better understanding of human DC.'