Tracing human dendritic cell development from a common precursor of dendritic cells and osteoclasts
. (LSBR 1355)
Project leaders: Prof. Dr. Jannie Borst and Dr. Yanling Xiao (Dept. of Immunology, NKI, Amsterdam)
Associate staff scientist: Yanling Xiao PhD (60% Aug. 2014 – Feb 2015 and 100% Mar. 2015 – July 2017)
Research technician: Joanna Grabowska MSc (Mar. 2015 – June 2017)
Dendritic cells (DCs), macrophages and osteoclasts (OCs) are very important cell types that are relevant in many diseases, including cancer and autoimmune diseases, such as rheumatoid arthritis. These cell types are closely related and stem from hematopoietic progenitors. However, the pathways of their development are not clear. Understanding this development and the signals involved is very important, because one can use that information to generate the cell types of interest in vitro, to use these cells for study or for therapy and to direct the development of these cell types purposely in a certain desired direction in disease.
The starting point of our project was that we had defined a population of cells in the mouse bone marrow that can form DCs and OCs. Genome-wide deep sequencing of mRNA revealed multiple molecules with defined or suspected roles in DC or OC development in mouse and human, including cell surface receptors. Our aim was to identify the equivalent progenitor in human and to find the appropriate cytokines and other requirements to culture functional DC subsets in vitro, from human progenitors found in BM and blood.
We have accomplished our goal and identified for the first time specific cell populations in human bone marrow and blood as progenitors of DCs. We have shown that these progenitor cells can also form monocytes/macrophages and OCs. We have identified many molecules that may direct the development of these cells. We have also developed a culture method to generate human DCs, which allows us to generate and study these very rare cells. We have also developed an in vitro system wherein we use these DCs to activate T cells. After further validation and extension, our results can be implemented in clinical diagnostics and therapy in many different ways.