Barbara Schraml
Klinikum der Universität München, Germany
Title: Defining Dendritic Cells by Ontogeny
Biography
Biography: Barbara Schraml
Abstract
Mononuclear phagocytes sample the environment for signs of damage or infection. The classification of these cells as macrophages or dendritic cells (DC) has traditionally been done on the basis of differences in cell morphology, expression of specific markers or of select functional attributes. However, these attributes are not absolute and often overlap, leading to difficulties in cell type identification. To circumvent these issues, we have generated a model to define DC based on their ontogenetic descendence from a committed precursor. We show that in mice precursors of conventional DC but not other leukocytes are marked by expression of DNGR-1/CLEC9A. We generated a mouse model to genetically label Clec9a-expressing conventional DC precursors and their progeny with yellow fluorescent protein (YFP). Genetic labeling of these cells and their progeny specifically traces cells traditionally ascribed to the DC lineage and the restriction is maintained after infection. Notably, in some tissues cells previously thought monocytes/macrophages are in fact descendants from DC precursors. These studies provide the first in vivo model for lineage tracing of DC and allow the definition of DC based on ontogenetic rather than phenotypic, morphological or functional criteria. These studies establish DC as an independent immune lineage and distinguish them from other leukocytes, thus paving the way to unraveling the functional complexity of the mononuclear phagocyte system.