Dendritic cells are versatile controllers of the immune system that sense pathogens and damage to initiate the bodies defense. They exist as developmentally distinct subsets with unique functions in immunity.
What determines dendritic cell function?
Dendritic cells are short lived and constantly replenished from bone marrow progenitors. We hypothesize that the cellular identity of dendritic cells is first imprinted by developmental origin (nature) and want to understand how it can be shaped environmental factors (nurture), such as the tissue microenvironment. To this end, we study how dendritic cell progenitors reach their target organs in steady state and during inflammation and identify the cell intrinsic and extrinsic signals that drive their terminal differentiation to establish tissue specific dendritic cell networks. We address our scientific questions in part using mouse models that allow for lineage tracing and visualization of dendritic cells based on their ontogenetic descendence from committed precursors, coupled to single cell technologies, transcriptomics and innovative imaging techniques. The tissue specific functions of dendritic cell subsets in immunity are further studied by depleting these cells and assessing subsequent immune responses.
The major challenges in the design of future therapies are to target specific components of the immune response in the absence of general immunosuppression. We think that understanding the unique functions of dendritic cells in the context of their microenvironment will help determine their potential to be targeted in immunotherapy. A better understanding of the development of dendritic cells may also help us identify factors that can be used to manipulate dendritic cell differentiation and function in vaccines or therapeutic settings.