1. Developmental Biology
  2. Immunology and Inflammation
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Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution

  1. Racquel Domingo-Gonzalez
  2. Fabio Zanini
  3. Xibing Che
  4. Min Liu
  5. Robert C Jones
  6. Michael A Swift
  7. Stephen R Quake  Is a corresponding author
  8. David N Cornfield  Is a corresponding author
  9. Cristina M Alvira  Is a corresponding author
  1. Stanford University School of Medicine, United States
  2. Stanford University, United States
  3. Chan Zuckerberg Biohub, United States
Research Article
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Cite this article as: eLife 2020;9:e56890 doi: 10.7554/eLife.56890

Abstract

At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Although many studies have focused on the adult lung, the perinatal lung remains unexplored. Here, we present an atlas of the murine lung immune compartment during early postnatal development. We show that the late embryonic lung is dominated by specialized proliferative macrophages with a surprising physical interaction with the developing vasculature. These macrophages disappear after birth and are replaced by a dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed an orchestration of distinct subpopulations across postnatal development to fill context-specific functions in tissue remodeling, angiogenesis, and immunity. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter immune cell phenotype during a period of rapid lung growth and heightened vulnerability.

Article and author information

Author details

  1. Racquel Domingo-Gonzalez

    Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Fabio Zanini

    Department of Bioengineering, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7097-8539
  3. Xibing Che

    Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Min Liu

    Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert C Jones

    Department of Bioengineering, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7235-9854
  6. Michael A Swift

    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephen R Quake

    Chan Zuckerberg Biohub, San Francisco, United States
    For correspondence
    steve@quake-lab.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1613-0809
  8. David N Cornfield

    Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
    For correspondence
    cornfield@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
  9. Cristina M Alvira

    Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
    For correspondence
    calvira@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6921-0001

Funding

National Institutes of Health (HL122918)

  • Cristina M Alvira

National Institutes of Health (HD092316)

  • David N Cornfield
  • Cristina M Alvira

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#19087) of Stanford University School of Medicine.

Reviewing Editor

  1. Emma L Rawlins, University of Cambridge, United Kingdom

Publication history

  1. Received: March 13, 2020
  2. Accepted: May 13, 2020
  3. Accepted Manuscript published: June 2, 2020 (version 1)

Copyright

© 2020, Domingo-Gonzalez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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