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Role and therapeutic potential of different skin and lymph node-resident dendritic cell subsets to control cutaneous leishmaniasis in mice

Subject Area Dermatology
Term from 2008 to 2016
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 55498437
 
Cutaneous leishmaniasis is one of the most frequent infectious diseases worldwide. Despite many efforts, a vaccine is not available yet. The main goal of the present project is a detailed characterization of the role of skin dendritic cell (DC) subsets in leishmaniasis. From our prior experiments, it became clear that different DC subsets in the skin play divergent roles during T cell priming and education, which is directly linked to different disease outcomes in experimental murine leishmaniasis. During the first 3 years of the project, we demonstrated that epidermal Langerhans cells (LC) regulate anti-Leishmania immunity by inducing regulatory T cells (Treg) that promote parasite persistence. This is most likely due to increased levels of IL-10. On the other hand, initial experiments using conditional cell ablation of other skin DC subsets revealed a protective role of dermal DC against L. major infection. Thus, in the present project we aim to (i) further characterize the DC subset mediating protection, (ii) determine the molecular mechanism how the DC subsets educate different T cell subtypes, and (iii) study if differences in the activation signal between the various skin DC subsets allow for selective targeting approaches in light of vaccine development.
DFG Programme Research Grants
International Connection Netherlands
Participating Person Professor Dr. Björn Clausen
 
 

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