Airway Injury Induces Alveolar Epithelial and Mesenchymal Responses Mediated by Macrophages

Overview

Journal bioRxiv

Date 2024 Apr 15

PMID 38617297

Authors

Irene G Wong

Jillian Stark

VanNashlee Ya

Aaron L Moye

Alan Baez Vazquez

Susanna M Dang

Andrea Shehaj

Maral J Rouhani

Roderick Bronson

Sam M Janes

Samuel P Rowbotham

Margherita Paschini

Ruth A Franklin

Carla F Kim

Affiliations

Soon will be listed here.

Abstract

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 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 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.

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