ArticleThe Journal of experimental medicine2013
Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04400929 (Using GM-CSF as a Host Directed Therapeutic Against COVID-19 - a Phase 2 Investigator Initiated Trial), which is not on this map. Cited by 774 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Using GM-CSF as a Host Directed Therapeutic Against COVID-19 - a Phase 2 Investigator Initiated Trial
Who cites it
774 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,217 citations in OpenAlex.
- The Role of Monocytes in the Natural History of Idiopathic Pulmonary Fibrosis: A Systematic Literature Review.International journal of molecular sciences · 2025Pooled it
- Research on tissue-resident macrophages in the field of cancer research: a bibliometric analysis from 2004 to 2025.Cell adhesion & migration · 2026Review
- Multi-level transcriptional control of specific macrophage responses.The EMBO journal · 2026Review
- Unraveling the Multifaceted Roles of Tissue-Resident Macrophages: Focus on Bone Homeostasis and Regeneration.Stem cell reviews and reports · 2026Review
- Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- Transmembrane delivery of antimicrobial peptides by engineered eCIS into macrophages for intracellular mycobacteria elimination.Science advances · 2026Article
- Plasticity of the infant immune system during the perinatal period.Nature reviews. Immunology · 2026Review
- Tissue-Resident Macrophages: Linking Physiology and Inflammation in Infection.Clinical reviews in allergy & immunology · 2026Review
- Article
- Macrophages are constitutive architects of tissue integrity.Nature reviews. Immunology · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Collaborative functionality between three types of inflammation in idiopathic pulmonary fibrosis.Nature immunology · 2026Review
- Induced pluripotent stem cell-derived macrophages (iMacs) in translational medicine: Disease models, drug testing, and therapeutic applications.Molecular biology reports · 2026Review
- Review
- Sex-specific in utero reprogramming of lung immunity.Mucosal immunology · 2026Article
- Alveolar macrophage-derived TGF-β promotes acute lung injury recovery by regulating inflammatory monocyte-derived macrophages.Journal of advanced research · 2026Article
- Neonatal hyperoxia promotes macrophage senescence and lung injury via a p38MAPK-dependent secretome.American journal of respiratory cell and molecular biology · 2026Article
- Differential activation of NF-Κβ and HIF-1α between fetal liver-derived and myeloid-derived macrophages drives inflammatory differences followingInfection and immunity · 2026Article
- Tissue-resident neutrophils serve homeostatic and immunological functions in embryos.Nature communications · 2026Article
- A signal-responsive cooperative transcription factor network determines alveolar macrophage identity.The Journal of experimental medicine · 2026Article
714 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.