Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia

Influenza A virus (IAV) infection mobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell...

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Published in:	Nature communications Vol. 15; no. 1; p. 87
Main Authors:	Pervizaj-Oruqaj, Learta, Selvakumar, Balachandar, Ferrero, Maximiliano Ruben, Heiner, Monika, Malainou, Christina, Glaser, Rolf David, Wilhelm, Jochen, Bartkuhn, Marek, Weiss, Astrid, Alexopoulos, Ioannis, Witte, Biruta, Gattenlöhner, Stefan, Vadász, István, Morty, Rory Edward, Seeger, Werner, Schermuly, Ralph Theo, Vazquez-Armendariz, Ana Ivonne, Herold, Susanne
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 02-01-2024 Nature Publishing Group Nature Portfolio
Subjects:	13 13/105 13/106 13/2 13/31 13/51 14/19 14/34 14/63 38/61 38/77 38/91 631/250/2504/342/1927 631/250/254 64/60 82/29 96/1 96/21 Animals Bone marrow Cell proliferation Colleges & universities Epithelial cells Epithelium Female Gene targeting Genes Homeostasis Hospitals Humanities and Social Sciences Humans Infections Inflammation Influenza Influenza A Influenza A virus Influenza, Human Internal medicine Lung Lung diseases Lungs Macrophages Macrophages, Alveolar Mice multidisciplinary Organoids Placenta Pneumonia Pneumonia, Viral Pregnancy Science Science (multidisciplinary) Stem cells Trachea Transcriptomics Viruses
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Summary:	Influenza A virus (IAV) infection mobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell transfer, and BMDM-specific gene targeting, we found that transitioning (“regenerative”) BMDM and TR-AM highly express Placenta-expressed transcript 1 (Plet1). We reveal that Plet1 is released from alveolar macrophages, and acts as important mediator of macrophage-epithelial cross-talk during lung repair by inducing proliferation of alveolar epithelial cells and re-sealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course attenuated viral lung injury and rescued mice from otherwise fatal disease, highlighting its therapeutic potential. Influenza virus infection causes injury to the lung. Here, Pervizaj-Oruqaj et al. show that Plet1 expressed by lung macrophages promotes epithelial repair by boosting epithelial cell proliferation and barrier function.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-023-44421-6