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Cooperation between the alveolar epithelium and lung-resident basophils shapes alveolar macrophages

Nature Reviews Immunology volume 21, page 344 (2021)Cite this article

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Alveolar macrophages are a subset of lung-resident phagocytes, derived from fetal liver monocytes that migrate to the alveolar niche and establish a highly functionalized pool. Although prior work has shown that these macrophages are dependent on granulocyte–macrophage colony-stimulating factor (GM-CSF), encoded by Csf2, and that the lung epithelium is a non-haematopoietic producer of the cytokine, it has remained unclear what intercellular crosstalk between immune cells and non-immune cells directs the development and maintenance of alveolar macrophages in the alveolar space.

In this preprint (not peer-reviewed), Gschwend et al. use lineage-tracing of GM-CSF-producing cells in the lungs (both haematopoietic cells and non-haematopoietic cells) to identify components of this intercellular crosstalk. They show that removal of GM-CSF production by alveolar type 2 epithelial cells precludes the establishment of a resident alveolar macrophage population during embryonic development and eliminates them in adult mice. This result shows for the first time the indispensable and non-redundant role of alveolar type 2 epithelial cells in controlling the population of lung-resident macrophages, despite the fact that these alveolar epithelial cells are not the greatest local producers of GM-CSF.

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  • Park, M. D. Oxford–Mount Sinai (OxMS) Preprint Journal Club. OxMS https://www.preprintclub.com/2021-april-gschwend (2021)

  • Cohen, M. et al. Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175, 1031–1044 (2018)

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  • Guilliams, M. et al. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J. Exp. Med. 210, 1977–1992 (2013)

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  1. OxMS Preprint Journal Club, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Matthew D. Park & Miriam Merad

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  1. Matthew D. Park
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  2. Miriam Merad
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Correspondence to Matthew D. Park or Miriam Merad.

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Park, M.D., Merad, M. Cooperation between the alveolar epithelium and lung-resident basophils shapes alveolar macrophages. Nat Rev Immunol 21, 344 (2021). https://doi.org/10.1038/s41577-021-00561-8

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