IL-1ß Promotes Expansion of IL-33+ Lung Epithelial Stem Cells after Respiratory Syncytial Virus Infection during Infancy.
Am J Respir Cell Mol Biol
; 66(3): 312-322, 2022 03.
Article
in En
| MEDLINE
| ID: mdl-34861136
ABSTRACT
Respiratory syncytial virus (RSV)-induced immunopathogenesis and disease severity in neonatal mice and human infants have been related to elevated pulmonary IL-33. Thus, targeting IL-33 has been suggested as a potential therapy for respiratory viral infections. Yet, the regulatory mechanisms on IL-33 during early life remain unclear. Here, using a neonatal mouse model of RSV, we demonstrate that IL-1ß positively regulates but is not required for RSV-induced expression of pulmonary IL-33 in neonatal mice early after the initial infection. Exogenous IL-1ß upregulates RSV-induced IL-33 expression by promoting the proliferation of IL-33+ lung epithelial stem/progenitor cells. These cells are exclusively detected in RSV-infected neonatal rather than adult mice, partially explaining the IL-1ß-independent IL-33 expression in RSV-infected adult mice. Furthermore, IL-1ß aggravates IL-33-mediated T-helper cell type 2-biased immunopathogenesis upon reinfection. Collectively, our study demonstrates that IL-1ß exacerbates IL-33-mediated RSV immunopathogenesis by promoting the proliferation of IL-33+ epithelial stem/progenitor cells in early life.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Syncytial Virus, Human
/
Respiratory Syncytial Virus Infections
/
Interleukin-1beta
Limits:
Animals
/
Humans
Language:
En
Journal:
Am J Respir Cell Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Document type:
Article