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Airway-associated macrophages in homeostasis and repair

View ORCID ProfileAnna E. Engler, View ORCID ProfileAlexandra B. Ysasi, View ORCID ProfileRiley M.F. Pihl, Carlos Villacorta-Martin, Hailey M. Heston, View ORCID ProfileHanne M.K. Richardson, Noah R. Moniz, View ORCID ProfileAnna C. Belkina, Sarah A. Mazzilli, View ORCID ProfileJason R. Rock
doi: https://doi.org/10.1101/2020.06.16.146035
Anna E. Engler
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Alexandra B. Ysasi
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Riley M.F. Pihl
2Flow Cytometry Core Facility, Boston University School of Medicine, Boston, MA, 02118, USA
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Carlos Villacorta-Martin
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Hailey M. Heston
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Hanne M.K. Richardson
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Noah R. Moniz
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Anna C. Belkina
2Flow Cytometry Core Facility, Boston University School of Medicine, Boston, MA, 02118, USA
3Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Sarah A. Mazzilli
4Department of Medicine and Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, 02118, USA
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Jason R. Rock
1Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA
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  • For correspondence: rockjr@bu.edu
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Summary

There is an increasing appreciation for the heterogeneity of myeloid lineages in the respiratory system, but whether distinct populations associate with the conducting airways remains unknown. 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 that are similar to lung interstitial macrophages and intraepithelial macrophages, and find that repair of the tracheal epithelium is impaired in Ccr2-deficient mice. Following injury there are early increases in neutrophils and submucosal macrophages, including M2-like macrophages. Unexpectedly, intraepithelial macrophages are initially lost but later replaced from CCR2+ monocytes. Mast cells and group 2 innate lymphoid cells are sources of IL13 that polarizes macrophages and directly influences basal cell behaviors. Their proximity to the airway epithelium establishes these myeloid populations as potential therapeutic targets for airway disease.

Competing Interest Statement

SAM received sponsored research funding from Janssen Pharmaceuticals.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 16, 2020.
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Airway-associated macrophages in homeostasis and repair
Anna E. Engler, Alexandra B. Ysasi, Riley M.F. Pihl, Carlos Villacorta-Martin, Hailey M. Heston, Hanne M.K. Richardson, Noah R. Moniz, Anna C. Belkina, Sarah A. Mazzilli, Jason R. Rock
bioRxiv 2020.06.16.146035; doi: https://doi.org/10.1101/2020.06.16.146035
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Airway-associated macrophages in homeostasis and repair
Anna E. Engler, Alexandra B. Ysasi, Riley M.F. Pihl, Carlos Villacorta-Martin, Hailey M. Heston, Hanne M.K. Richardson, Noah R. Moniz, Anna C. Belkina, Sarah A. Mazzilli, Jason R. Rock
bioRxiv 2020.06.16.146035; doi: https://doi.org/10.1101/2020.06.16.146035

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