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Cell Stem Cell. 2017 Jul 6;21(1):120-134.e7. doi: 10.1016/j.stem.2017.03.024. Epub 2017 May 11.

Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.

Author information

1
Department of Anatomy, University of California, San Francisco, CA 94143, USA.
2
Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
3
Department of Anatomy, University of California, San Francisco, CA 94143, USA. Electronic address: rockjr@bu.edu.

Abstract

To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes. Our data suggest that these cells modulate AEC2 proliferation and differentiation. Finally, we provide evidence that group 2 innate lymphoid cells are a source of IL-13, which promotes lung regeneration. Together, our data highlight the potential for immunomodulatory therapies to stimulate alveologenesis in adults.

KEYWORDS:

ILC2; lung regeneration; macrophage; monocyte; pneumonectomy; type 2 alveolar pneumocyte

Comment in

PMID:
28506464
PMCID:
PMC5501755
DOI:
10.1016/j.stem.2017.03.024
[Indexed for MEDLINE]
Free PMC Article

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