IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells.
Cell Rep
; 43(8): 114569, 2024 Aug 27.
Article
in En
| MEDLINE
| ID: mdl-39088319
ABSTRACT
Wound healing in response to acute injury is mediated by the coordinated and transient activation of parenchymal, stromal, and immune cells that resolves to homeostasis. Environmental, genetic, and epigenetic factors associated with inflammation and aging can lead to persistent activation of the microenvironment and fibrosis. Here, we identify opposing roles of interleukin-4 (IL-4) cytokine signaling in interstitial macrophages and type II alveolar epithelial cells (ATIIs). We show that IL4Ra signaling in macrophages promotes regeneration of the alveolar epithelium after bleomycin-induced lung injury. Using organoids and mouse models, we show that IL-4 directly acts on a subset of ATIIs to induce the expression of the transcription factor SOX9 and reprograms them toward a progenitor-like state with both airway and alveolar lineage potential. In the contexts of aging and bleomycin-induced lung injury, this leads to aberrant epithelial cell differentiation and bronchiolization, consistent with cellular and histological changes observed in interstitial lung disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bleomycin
/
Interleukin-4
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Cell Lineage
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SOX9 Transcription Factor
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Lung
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
/
Cell reports
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: