The heterogeneity of lung macrophages in the susceptibility to disease.
Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and/or replace its composition. The signals that induce the recruitment of circulating monocytes to the injured lung, as well as their distinct gene expression profile and susceptibility to epigenetic reprogramming by the local environment remain unclear. In this review, we summarise the unique characteristics of the alveolar macrophage pool ontogeny, phenotypic heterogeneity and plasticity during homeostasis, tissue injury and normal ageing. We also discuss new evidence arising from recent studies where investigators described how the epigenetic landscape drives the specific gene expression profile of alveolar macrophages. Altogether, new analysis of macrophages by means of "omic" technologies will allow us to identify key pathways by which these cells contribute to the development and resolution of lung disease in both mice and humans.
Dept of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Luisa
L
Morales-Nebreda
Dept of Medicine, Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Alexander V
AV
Misharin
Dept of Medicine, Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Harris
H
Perlman
Dept of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA s-buding@northwestern.edu.
G R Scott
GR
Budinger
D000818:Animals; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D060833:Cellular Microenvironment; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012307:Risk Factors