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Content archived on 2024-05-29

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

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 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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Call for proposal

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FP7-PEOPLE-IEF-2008
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

CANCER RESEARCH UK LBG
EU contribution
€ 180 783,75
Address
2 Redman Place
E20 1JQ LONDON
United Kingdom

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Region
London Inner London — East Hackney and Newham
Activity type
Research Organisations
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Total cost

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