title: Identification and Characterization of a Dendritic Cell Precursor in Parenchymal Lung Tissue.
abstract: 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 (PC) 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 PC and showed that it had rapid depletion and reconstitution kinetics that were similar to those of DC, with a 50% repopulation by donor-derived cells by Days 7-9 after reconstitution. This was significantly faster than the rates observed for mø, which showed 50% repopulation by donor-derived cells beyond Days 16-21 after reconstitution. Purified PC gained antigen-presenting function and a cell surface phenotype similar to that of pulmonary DC after maturation in vitro, with light and electron microscopy confirming a myeloid DC morphology. To the best of our knowledge, this is the first study to describe a PC for DC in lung tissue; the findings have implications for the restoration of pulmonary immunological homeostasis after bone marrow transplant.
authors: 1 Respiratory Medicine, Department of Clinical Research, Bern University Hospital, Bern, Switzerland.
authors: Christophe
authors: C
authors: von Garnier
authors: 1 Respiratory Medicine, Department of Clinical Research, Bern University Hospital, Bern, Switzerland.
authors: Fabian
authors: F
authors: Blank
authors: 2 Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland.
authors: Barbara
authors: B
authors: Rothen-Rutishauser
authors: 3 Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany.
authors: Joachim R
authors: JR
authors: Goethert
authors: 4 Telethon Kids Institute, Perth, Australia.
authors: Patrick G
authors: PG
authors: Holt
authors: 4 Telethon Kids Institute, Perth, Australia.|5 School of Veterinary and Life Sciences, Murdoch University, Perth, Australia; and.|6 School of Pediatrics and Child Health, The University of Western Australia, Perth, Australia.
authors: Philip A
authors: PA
authors: Stumbles
authors: 4 Telethon Kids Institute, Perth, Australia.
authors: Deborah H
authors: DH
authors: Strickland
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000166:cytology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D015415:Biomarkers; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: bone marrow; dendritic cell; lung; mouse; precursor