title: Three Unique Interstitial Macrophages in the Murine Lung at Steady State.
abstract: The current paradigm in macrophage biology is that some tissues mainly contain macrophages from embryonic origin, such as microglia in the brain, whereas other tissues contain postnatal-derived macrophages, such as the gut. However, in the lung and in other organs, such as the skin, there are both embryonic and postnatal-derived macrophages. In this study, we demonstrate in the steady-state lung that the mononuclear phagocyte system is comprised of three newly identified interstitial macrophages (IMs), alveolar macrophages, dendritic cells, and few extravascular monocytes. We focused on similarities and differences between the three IM subtypes, specifically, their phenotype, location, transcriptional signature, phagocytic capacity, turnover, and lack of survival dependency on fractalkine receptor, CX3CR1. Pulmonary IMs were located in the bronchial interstitium but not the alveolar interstitium. At the transcriptional level, all three IMs displayed a macrophage signature and phenotype. All IMs expressed MER proto-oncogene, tyrosine kinase, CD64, CD11b, and CX3CR1, and were further distinguished by differences in cell surface protein expression of CD206, Lyve-1, CD11c, CCR2, and MHC class II, along with the absence of Ly6C, Ly6G, and Siglec F. Most intriguingly, in addition to the lung, similar phenotypic populations of IMs were observed in other nonlymphoid organs, perhaps highlighting conserved functions throughout the body. These findings promote future research to track four distinct pulmonary macrophages and decipher the division of labor that exists between them.
authors.affiliation: 1 Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Gibbings
authors.affiliation: 1 Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Thomas
authors.affiliation: 1 Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Atif
authors.affiliation: 2 Department of Medicine, National Jewish Health, Denver, Colorado.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: McCubbrey
authors.affiliation: 3 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver Anschutz Campus, Denver, Colorado.
authors.forename: A Nicole
authors.initials: AN
authors.lastname: Desch
authors.affiliation: 4 Integrated Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Danhorn
authors.affiliation: 4 Integrated Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado; and.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Leach
authors.affiliation: 3 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver Anschutz Campus, Denver, Colorado.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Bratton
authors.affiliation: 1 Department of Pediatrics, National Jewish Health, Denver, Colorado.|3 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver Anschutz Campus, Denver, Colorado.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.affiliation: 2 Department of Medicine, National Jewish Health, Denver, Colorado.|5 Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Denver, Colorado.
authors.forename: William J
authors.initials: WJ
authors.lastname: Janssen
authors.affiliation: 1 Department of Pediatrics, National Jewish Health, Denver, Colorado.|3 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver Anschutz Campus, Denver, Colorado.
authors.forename: Claudia V
authors.initials: CV
authors.lastname: Jakubzick
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D008168:Lung / Q000166:cytology*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D014158:Transcription, Genetic
keywords: dendritic cells; interstitial macrophages; monocytes; mononuclear phagocytes; pulmonary