title: Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF.
abstract: Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac-derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80(hi)CD11b(lo) primitive macrophages and Ly6C(hi)CD11b(hi) fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF-deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life.
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9050 Ghent, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
authors.forename: Ismé
authors.initials: I
authors.lastname: De Kleer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.forename: Sijranke
authors.initials: S
authors.lastname: Post
authors.forename: Leen
authors.initials: L
authors.lastname: Vanhoutte
authors.forename: Sofie
authors.initials: S
authors.lastname: De Prijck
authors.forename: Kim
authors.initials: K
authors.lastname: Deswarte
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology / Q000528:radiation effects; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D014916:Whole-Body Irradiation
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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