Dataset Information

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

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.

SUBMITTER: Lechner AJ

PROVIDER: S-EPMC5501755 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Lechner Andrew J AJ Driver Ian H IH Lee Jinwoo J Conroy Carmen M CM Nagle Abigail A Locksley Richard M RM Rock Jason R JR

Cell stem cell 20170511 1

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) tra ...[more]

PMID: 28506464

Similar Datasets

Project description:The adult human lung has a very limited capacity to regenerate functional alveoli. In contrast, adult mice have a remarkable capacity for neoalveolarization following either lung resection or injury. The molecular basis for this unique capability to regenerate lung tissue in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling used in this species during lung regeneration. Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology. The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts, up-regulation of genes involved in T cell development and function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This appears to differ from embryonic alveologenesis. These data suggest that modulation of mesenchymal cell signaling and proliferation may act in concert with immunomodulation to control inflammation during post-pneumonectomy lung regeneration in adult mice. Experiment Overall Design: For each of the four time points (6 hr, 1 day, 3 day, 7 day), the mice were divided into two groups: (1) pneumonectomy (PNY) and (2) sham operated (SHAM - thoracotomy without lung resection), with eight animals in each group. One microarray was performed on pooled lung tissue from these 8 animals for each time point. Analysis of expression in PNY vs SHAM animals was performed in two ways: using all four microarrays as replicates in a time-independent analysis, as well as analysis of each time point separately (time-dependent) without replicates.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure