Identification and Characterization of a Dendritic Cell Precursor in Parenchymal Lung Tissue.

The pulmonary parenchymal and mucosal microenvironments are constantly exposed to the external environment and thus require continuous surveillance to maintain steady-state immunological homeostasis. This is achieved by a mobile network of pulmonary dendritic cells (DC) and macrophages (mø) that constantly sample and process microenvironmental antigens into signals that can initiate or dampen inflammation, either locally or after onward migration to draining lymph nodes. The constant steady-state turnover of pulmonary DC and mø requires replenishment from bone-marrow precursors, however the nature of the pulmonary precursor cell remains unclear, although recent studies suggest that subsets of pulmonary DC may derive from circulating monocytic precursors. In the current study, we describe a population of cells in steady-state mouse lung tissue that has the surface phenotypic and ultrastructural characteristics of a common DC progenitor. Irradiation and reconstitution studies confirmed the bone-marrow origins of this precursor cell (PC), and showed that it had rapid depletion and reconstitution kinetics that were similar to DC, with a 50% repopulation by donor-derived cells by days 7-9 post-reconstitution. This was significantly faster than the rates observed for mø, which showed 50% repopulation by donor-derived cells beyond days 16-21 post-reconstitution. Purified PC gained antigen presenting function and cell surface phenotype similar to pulmonary DC after maturation in vitro, with light and electron microscopy confirming a myeloid DC morphology. This is the first study to describe a precursor cell for DC in lung tissue, and has implications for restoration of pulmonary immunological homeostasis after bone marrow transplantation.