PMID- 28506464 OWN - NLM STAT- MEDLINE DCOM- 20180322 LR - 20181113 IS - 1875-9777 (Electronic) IS - 1934-5909 (Print) IS - 1875-9777 (Linking) VI - 21 IP - 1 DP - 2017 Jul 6 TI - Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy. PG - 120-134.e7 LID - S1934-5909(17)30095-4 [pii] LID - 10.1016/j.stem.2017.03.024 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Lechner, Andrew J AU - Lechner AJ AD - Department of Anatomy, University of California, San Francisco, CA 94143, USA. FAU - Driver, Ian H AU - Driver IH AD - Department of Anatomy, University of California, San Francisco, CA 94143, USA. FAU - Lee, Jinwoo AU - Lee J AD - Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA. FAU - Conroy, Carmen M AU - Conroy CM AD - Department of Anatomy, University of California, San Francisco, CA 94143, USA. FAU - Nagle, Abigail AU - Nagle A AD - Department of Anatomy, University of California, San Francisco, CA 94143, USA. FAU - Locksley, Richard M AU - Locksley RM AD - Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA. FAU - Rock, Jason R AU - Rock JR AD - Department of Anatomy, University of California, San Francisco, CA 94143, USA. Electronic address: rockjr@bu.edu. LA - eng GR - T32 GM007618/GM/NIGMS NIH HHS/United States GR - P01 HL107202/HL/NHLBI NIH HHS/United States GR - R01 HL127002/HL/NHLBI NIH HHS/United States GR - R01 HL128903/HL/NHLBI NIH HHS/United States GR - F30 HL131198/HL/NHLBI NIH HHS/United States GR - U01 HL134766/HL/NHLBI NIH HHS/United States GR - R37 AI026918/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170511 PL - United States TA - Cell Stem Cell JT - Cell stem cell JID - 101311472 RN - 0 (Ccr2 protein, mouse) RN - 0 (Il4ra protein, mouse) RN - 0 (Interleukin-13) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Cell Surface) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) SB - IM CIN - Stem Cell Investig. 2018 Mar 31;5:8. PMID: 29682515 MH - Animals MH - Interleukin-13/genetics/immunology MH - Lung/*physiology MH - Macrophages, Alveolar/*immunology MH - Mice MH - Mice, Knockout MH - Monocytes/*immunology MH - *Pneumonectomy MH - Receptor, Macrophage Colony-Stimulating Factor/genetics/immunology MH - Receptors, CCR2/genetics/immunology MH - Receptors, Cell Surface/genetics/immunology MH - Regeneration/genetics/*immunology MH - Th2 Cells/*immunology PMC - PMC5501755 MID - NIHMS864448 OTO - NOTNLM OT - ILC2 OT - lung regeneration OT - macrophage OT - monocyte OT - pneumonectomy OT - type 2 alveolar pneumocyte EDAT- 2017/05/17 06:00 MHDA- 2018/03/23 06:00 PMCR- 2018/07/06 CRDT- 2017/05/17 06:00 PHST- 2016/08/19 00:00 [received] PHST- 2017/02/09 00:00 [revised] PHST- 2017/03/27 00:00 [accepted] PHST- 2017/05/17 06:00 [pubmed] PHST- 2018/03/23 06:00 [medline] PHST- 2017/05/17 06:00 [entrez] PHST- 2018/07/06 00:00 [pmc-release] AID - S1934-5909(17)30095-4 [pii] AID - 10.1016/j.stem.2017.03.024 [doi] PST - ppublish SO - Cell Stem Cell. 2017 Jul 6;21(1):120-134.e7. doi: 10.1016/j.stem.2017.03.024. Epub 2017 May 11.