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Παρασκευή 12 Μαΐου 2017

Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy

Publication date: Available online 11 May 2017
Source:Cell Stem Cell
Author(s): Andrew J. Lechner, Ian H. Driver, Jinwoo Lee, Carmen M. Conroy, Abigail Nagle, Richard M. Locksley, Jason R. Rock
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.

Graphical abstract

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Teaser

Lechner et al. identify regenerative myeloid subpopulations, including recruited CCR2+ monocytes and Arginase1+ macrophages, during pneumonectomy-induced lung regeneration. Loss of recruited monocytes or Il4ra signaling impaired lung regeneration. The authors provide evidence that ILC2s and lung macrophages modulate the regenerative microenvironment to support alveolar epithelial stem cell proliferation and differentiation.


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