Airway-Associated Macrophages in Homeostasis and Repair

Cell Rep. 2020 Dec 29;33(13):108553. doi: 10.1016/j.celrep.2020.108553.


There is an increasing appreciation for the heterogeneity of myeloid lineages in the lung, but relatively little is known about populations specifically associated with the conducting airways. We use single-cell RNA sequencing, flow cytometry, and immunofluorescence to characterize myeloid cells of the mouse trachea during homeostasis and epithelial injury/repair. We identify submucosal macrophages, similar to lung interstitial macrophages, and intraepithelial macrophages. Following injury, there are early increases in neutrophils and submucosal macrophages, including M2-like macrophages. Intraepithelial macrophages are lost after injury and later restored by CCR2+ monocytes. We show that repair of the tracheal epithelium is impaired in Ccr2-deficient mice. Mast cells and group 2 innate lymphoid cells are sources of interleukin-13 (IL-13) that polarize macrophages and directly influence basal cell behaviors. Their proximity to the airway epithelium establishes these myeloid populations as potential therapeutic targets for airway disease.

Keywords: airway; macrophages; niche; regeneration; trachea.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / metabolism
  • Epithelial Cells / metabolism*
  • Epithelium / injuries
  • Epithelium / metabolism*
  • Female
  • Homeostasis*
  • Lung / metabolism
  • Lung Injury / chemically induced
  • Macrophages, Alveolar / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Monocytes / metabolism
  • Myeloid Cells / physiology*
  • Polidocanol
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism*
  • Regeneration
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Trachea / injuries
  • Trachea / metabolism*


  • Ccr2 protein, mouse
  • Cytokines
  • Receptors, CCR2
  • Polidocanol