Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection.
Andrew K BeppuJuanjuan ZhaoChangfu YaoGianni CarraroEdo IsraelyAnna Lucia CoelhoKatherine DrakeCory M HogaboamWilliam C ParksJay K KollsBarry R StrippPublished in: Nature communications (2023)
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.
Keyphrases
- innate immune
- stem cells
- lung function
- induced apoptosis
- poor prognosis
- cystic fibrosis
- cell cycle arrest
- oxidative stress
- chronic obstructive pulmonary disease
- cell therapy
- rheumatoid arthritis
- staphylococcus aureus
- high grade
- air pollution
- endoplasmic reticulum stress
- signaling pathway
- single cell
- genome wide
- type diabetes
- copy number
- cell death
- minimally invasive
- high glucose
- binding protein
- metabolic syndrome
- room temperature
- ankylosing spondylitis
- dna methylation
- interstitial lung disease
- insulin resistance