Cel Dendritic cells (DC) are a heterogeneous family of leucocytes with important functions in immunity. Little is known about the role of distinct DC subtypes in vivo. In the mouse, a subset known as CD8alpha+ DC has been argued to represent a discrete DC lineage with specialised properties. These include a superior capacity for presenting exogenous antigens to CD8+ and CD4+ T cells, which makes CD8alpha+ DC an attractive target in vaccination and tolerisation. However, it is unclear whether CD8alpha+ DC fulfill unique and non-redundant roles in the immune system. In addition, the reported restriction of CD8alpha+ DC to thymus and secondary lymphoid organs is hard to reconcile with their documented capacity to act as presenting cells for antigens outside those organs. Finally, CD8alpha+ DC have not been identified in humans, greatly restricting their use in immunotherapy. In this proposal, we exploit the recent finding that DNGR-1 (CLEC9A) acts as a new and specific marker for the CD8alpha+ lineage to address these issues. We will generate DNGR-1-Cre mice as a universal tool to manipulate gene expression in the subset. We will use such mice to render CD8alpha+ DC sensitive to toxic proteins that permit constitutive or transient ablation of the subset for functional studies. DNGR-1-Cre mice will further be used to express fluorescent proteins in CD8alpha+ DC, allowing tracing of the lineage in vivo, both in lymphoid and non-lymphoid organs. Finally, we will use the DNGR-1 marker to identify and characterise putative CD8alpha+ DC equivalents in humans. The results from this proposal will illuminate the function of CD8alpha+ DC across species and open the door for using this intriguing DC subset in immunotherapy of cancer, infectious and autoimmune diseases. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Program(-y) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Zaproszenie do składania wniosków ERC-2010-AdG_20100317 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-AG - ERC Advanced Grant Instytucja przyjmująca THE FRANCIS CRICK INSTITUTE LIMITED Wkład UE € 2 499 998,20 Adres 1 MIDLAND ROAD NW1 1AT London Zjednoczone Królestwo Zobacz na mapie Region London Inner London — West Camden and City of London Rodzaj działalności Research Organisations Kontakt administracyjny Stéphane Maikovsky (Mr.) Kierownik naukowy Caetano Maria Pacheco Pais Dos Reis E Sousa (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (2) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko THE FRANCIS CRICK INSTITUTE LIMITED Zjednoczone Królestwo Wkład UE € 2 499 998,20 Adres 1 MIDLAND ROAD NW1 1AT London Zobacz na mapie Region London Inner London — West Camden and City of London Rodzaj działalności Research Organisations Kontakt administracyjny Stéphane Maikovsky (Mr.) Kierownik naukowy Caetano Maria Pacheco Pais Dos Reis E Sousa (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych CANCER RESEARCH UK LBG Zjednoczone Królestwo Wkład UE Brak danych Adres 2 Redman Place E20 1JQ LONDON Zobacz na mapie Region London Inner London — West Camden and City of London Rodzaj działalności Research Organisations Kontakt administracyjny Holly Elphinstone (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych