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CD8DC FUNCTIONS

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DNRG 1 as a marker to develop better models for characterising human and mouse d...

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

30/09/2011

CR-UK

181K€

Presupuesto del proyecto: 181K€

Líder del proyecto

CANCER RESEARCH UK LBG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2011-09-30 No tenemos la información de la convocatoria

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CR-UK

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Líder del proyecto

CANCER RESEARCH UK LBG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 181K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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 CD8+DC and then, we believe that it constitutes a better marker for CD8+DC 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 CD8+DC 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 CD8+DC. The function of CD8+DC 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 CD8+DC. 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 CD8+DC. This model will allows us to assess the effect of ablation of CD8+DC on the immune system. In humans, it has been argued that CD8+DC 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 CD8+DC. Then, we plan to characterise the functional properties of human DNGR-1+DC in detail and determine whether they match those expected from the study of murine CD8+DC. 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.

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