[PDF][PDF] Recruited monocytes and type 2 immunity promote lung regeneration following pneumonectomy

AJ Lechner, IH Driver, J Lee, CM Conroy, A Nagle… - Cell stem cell, 2017 - cell.com
AJ Lechner, IH Driver, J Lee, CM Conroy, A Nagle, RM Locksley, JR Rock
Cell stem cell, 2017cell.com
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 …
Summary
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.
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