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Role of plasmacytoid dendritic cells in the orchestration of in vivo immune responses (ORCHESTRATE)
Start date: Dec 1, 2012, End date: Nov 30, 2014 PROJECT  FINISHED 

"Plasmacytoid dendritic cells (pDCs) which are professional type I IFN producing cells modulate phenotype and function of conventional dendritic cells (cDCs) triggering maturation and enhancing priming of cytotoxic T lymphocytes (CTLs). It is widely accepted that type I IFNs offer a link between innate and adaptive immune responses, but there are contrasting data regarding their immunoregulatory effects. It has been shown that pDC derived IFNs modulate the phenotype and function of conventional DCs. Moreover, pDCs and cDCs contribute to the activation of NK cells. Ability of pDC to function as APC for T cells is also demonstrated. Thus pDC appear specialized for initiation of innate response, but also have certain capabilities of inducing and modulating adaptive immune responses.Recent work from Albert group provided a first-generation multi-analyte profile (MAP) of how pDCs serve to bridge innate and adaptive immune responses in the context of TLR7 and TLR9 agonists analysing in vitro human isolated pDCs. Four distinct cytokine/chemokine loops by wich pDCs contribute to the initiation of an inflammatory response were identified, what helped to provide a foundation for understanding the functional status of pDCs in different disease states.To understand the impact of inflammatory response on the coordination of immune responses, to define the mechanism by which innate effector molecules influence adaptive immunity at a fundamental level, in vivo research on mouse models is required. Thusfar mice strain that permit control of gene expression in pDCs has not been used. The Albert lab developed Siglec-H-CreERT2 knock-in mice with pDC specific inducible Cre expression. A second knock-in was developed in order to control the production of type I IFNs – Siglec-H-IRF-7. By using new mice mutants it will be possible to determine the role of pDCs and pDC-derived type I IFNs in the orchestration of cDC activation of CD8+ T cell and NK cell responses in vivo."
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