Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection

Epithelial plasticity has been suggested in lungs of mice following genetic depletion of stem cells but is of unknown physiological relevance. Viral infection and chronic lung disease share similar pathological features of stem cell loss in alveoli, basal cell (BC) hyperplasia in small airways, and...

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Published in:Nature communications 2023-09, Vol.14 (1), p.5814-16, Article 5814
Main Authors: Beppu, Andrew K., Zhao, Juanjuan, Yao, Changfu, Carraro, Gianni, Israely, Edo, Coelho, Anna Lucia, Drake, Katherine, Hogaboam, Cory M., Parks, William C., Kolls, Jay K., Stripp, Barry R.
Format: Article
Language:English
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Alveoli
Animals
Cell Differentiation
Chronic infection
Epithelial Cells
Epithelium
Gas exchange
Humanities and Social Sciences
Hyperplasia
Immune response
Immunity, Innate
Infections
Lung diseases
Mice
multidisciplinary
Plastic properties
Plasticity
Pulmonary Alveoli
Respiratory function
Respiratory tract
Science
Science (multidisciplinary)
Stem cells
Transcriptomics
Viral infections
Viruses
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Summary:Epithelial plasticity has been suggested in lungs of mice following genetic depletion of stem cells but is of unknown physiological relevance. Viral infection and chronic lung disease share similar pathological features of stem cell loss in alveoli, basal cell (BC) hyperplasia in small airways, and innate immune activation, that contribute to epithelial remodeling and loss of lung function. We show that a subset of distal airway secretory cells, intralobar serous (IS) cells, are activated to assume BC fates following influenza virus infection. Injury-induced hyperplastic BC (hBC) differ from pre-existing BC by high expression of IL-22Ra1 and undergo IL-22-dependent expansion for colonization of injured alveoli. Resolution of virus-elicited inflammation results in BC to IS re-differentiation in repopulated alveoli, and increased local expression of protective antimicrobial factors, but fails to restore normal alveolar epithelium responsible for gas exchange. After respiratory viral infection and in fibrotic lung disease, repair and remodeling processes particularly affect airway basal cell (BC) and alveolar epithelial cell populations. Here, using single cell transcriptomics and lineage tracing, the authors characterize this process and define roles for innate immune activation in the regulation of BC fate and alveolar remodeling.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-41387-3