Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages.

Autor:	Wong IG; Harvard University, Cambridge, MA 02138, USA.; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Stark J; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Harvard College, Cambridge, MA 02138, USA., Ya V; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Moye AL; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Vazquez AB; Harvard University, Cambridge, MA 02138, USA.; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA., Dang SM; Harvard University, Cambridge, MA 02138, USA.; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Shehaj A; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Rouhani MJ; UCL Respiratory, Division of Medicine, University College London, London, UK., Bronson R; Rodent Histopathology Core, Harvard Medical School, Boston, MA 02115, USA., Janes SM; UCL Respiratory, Division of Medicine, University College London, London, UK., Rowbotham SP; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Pediatric Surgical Research Laboratories, Mass. General Hospital, Boston MA 02114 USA. Department of Surgery, Harvard Medical School, Boston MA 02115., Paschini M; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Franklin RA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Kim CF; Stem Cell Program, Division of Hematology/Oncology and Pulmonary & Respiratory Diseases, Children's Hospital Boston, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 02. Date of Electronic Publication: 2024 May 02.
DOI:	10.1101/2024.04.02.587596
Abstrakt:	Acute injury in the airways or the lung activates local progenitors and stimulates changes in cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted. We utilized mouse models of airway-specific epithelial injury to examine secondary tissue-wide alveolar, immune, and mesenchymal responses. Single-cell transcriptomics and in vivo validation revealed transient, tissue-wide proliferation of alveolar type 2 (AT2) progenitor cells after club cell-specific ablation. The AT2 cell proliferative response was reliant on alveolar macrophages (AMs) via upregulation of Spp1 which encodes the secreted factor Osteopontin. A previously uncharacterized mesenchymal population we termed Mesenchymal Airway/Adventitial Niche Cell 2 (MANC2) also exhibited dynamic changes in abundance and a pro-fibrotic transcriptional signature after club cell ablation in an AM-dependent manner. Overall, these results demonstrate that acute airway damage can trigger distal lung responses including altered cell-cell interactions that may contribute to potential vulnerabilities for further dysregulation and disease. Competing Interests: Competing Interests C.F.K. had a sponsored research agreement with Celgene/BMS Corporation during part of the period of these studies, yet the work in that agreement did not overlap with this study. C.F.K. and A.L.M. are founders of Cellforma. I.G.W. and all other authors declare no competing interests.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu