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

Andrew K Beppu; Juanjuan Zhao; Changfu Yao; Gianni Carraro; Edo Israely; Anna Lucia Coelho; Katherine Drake; Cory M Hogaboam; William C Parks; Jay K Kolls; Barry R Stripp

doi:10.1038/s41467-023-41387-3

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

Nat Commun. 2023 Sep 19;14(1):5814. doi: 10.1038/s41467-023-41387-3.

Authors

Andrew K Beppu^#^{1

2

3}, Juanjuan Zhao^#^{1

2

3}, Changfu Yao^{1

2

3}, Gianni Carraro^{1

2

3}, Edo Israely³, Anna Lucia Coelho^{1

2}, Katherine Drake^{1

2

3}, Cory M Hogaboam^{1

2}, William C Parks^{1

2}, Jay K Kolls⁴, Barry R Stripp^{5

6

7}

Affiliations

¹ Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
² Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
³ Department of Medicine, Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
⁴ Tulane Center for Translational Research in Infection and Inflammation, School of Medicine, New Orleans, LA, 70112, USA.
⁵ Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. barry.stripp@csmc.edu.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. barry.stripp@csmc.edu.
⁷ Department of Medicine, Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. barry.stripp@csmc.edu.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Epithelial Cells*
Hyperplasia
Immunity, Innate
Mice
Pulmonary Alveoli*

Abstract

Publication types

MeSH terms

Grants and funding