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

Learta Pervizaj-Oruqaj; Balachandar Selvakumar; Maximiliano Ruben Ferrero; Monika Heiner; Christina Malainou; Rolf David Glaser; Jochen Wilhelm; Marek Bartkuhn; Astrid Weiss; Ioannis Alexopoulos; Biruta Witte; Stefan Gattenlöhner; István Vadász; Rory Edward Morty; Werner Seeger; Ralph Theo Schermuly; Ana Ivonne Vazquez-Armendariz; Susanne Herold

doi:10.1038/s41467-023-44421-6

Nature Communications (Jan 2024)

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

Learta Pervizaj-Oruqaj,
Balachandar Selvakumar,
Maximiliano Ruben Ferrero,
Monika Heiner,
Christina Malainou,
Rolf David Glaser,
Jochen Wilhelm,
Marek Bartkuhn,
Astrid Weiss,
Ioannis Alexopoulos,
Biruta Witte,
Stefan Gattenlöhner,
István Vadász,
Rory Edward Morty,
Werner Seeger,
Ralph Theo Schermuly,
Ana Ivonne Vazquez-Armendariz,
Susanne Herold

Affiliations

Learta Pervizaj-Oruqaj: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Balachandar Selvakumar: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Maximiliano Ruben Ferrero: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Monika Heiner: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Christina Malainou: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Rolf David Glaser: Institute for Lung Health (ILH), Justus Liebig University
Jochen Wilhelm: Institute for Lung Health (ILH), Justus Liebig University
Marek Bartkuhn: Institute for Lung Health (ILH), Justus Liebig University
Astrid Weiss: Excellence Cluster Cardio-Pulmonary Institute (CPI)
Ioannis Alexopoulos: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Biruta Witte: Department of General and Thoracic Surgery, University Hospital of Giessen
Stefan Gattenlöhner: Department of Pathology, University Hospital of Giessen
István Vadász: Institute for Lung Health (ILH), Justus Liebig University
Rory Edward Morty: Department of Translational Pulmonology and the Translational Lung Research Center, University Hospital Heidelberg, Member of the German Center for Lung Research (DZL)
Werner Seeger: Institute for Lung Health (ILH), Justus Liebig University
Ralph Theo Schermuly: Institute for Lung Health (ILH), Justus Liebig University
Ana Ivonne Vazquez-Armendariz: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)
Susanne Herold: Department of Internal Medicine V, Universities of Giessen and Marburg Lung Center, University Hospital Giessen, Justus Liebig University, Member of the German Center for Lung Research (DZL)

DOI: https://doi.org/10.1038/s41467-023-44421-6
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 19

Abstract

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Abstract 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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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