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

Von Garnier, Christophe; Blank, Fabian; Rothen-Rutishauser, Barbara; Goethert, Joachim R; Holt, Patrick G; Stumbles, Philip A; Strickland, Deborah H (2017). Identification and Characterization of a Dendritic Cell Precursor in Parenchymal Lung Tissue. American journal of respiratory cell and molecular biology, 56(3), pp. 353-361. American Lung Association 10.1165/rcmb.2016-0058OC

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
09 Interdisciplinary Units > Microscopy Imaging Center MIC
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Live Cell Imaging (LCI)

UniBE Contributor:

Von Garnier, Christophe and Blank, Fabian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1044-1549

Publisher:

American Lung Association

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

28 Feb 2017 11:27

Last Modified:

19 Feb 2019 14:47

Publisher DOI:

10.1165/rcmb.2016-0058OC

PubMed ID:

27779901

Uncontrolled Keywords:

Dendritic cell; bone marrow; lung; mouse; precursor

URI:

https://boris.unibe.ch/id/eprint/93252

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