Title

IL-1 beta Promotes Expansion of IL-33(+) Lung Epithelial Stem Cells after Respiratory Syncytial Virus Infection during Infancy

Document Type

Article

Publication Date

3-2022

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-1 beta positively regulates but is not required for RSV-induced expression of pulmonary IL-33 in neonatal mice early after the initial infection. Exogenous IL-1 beta 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-1 beta-independent IL-33 expression in RSV-infected adult mice. Furthermore, IL-10 aggravates IL-33-mediated T- helper cell type 2-biased immunopathogenesis upon reinfection. Collectively, our study demonstrates that IL-1 beta exacerbates IL-33-mediated RSV immunopathogenesis by promoting the proliferation of IL-33(+) epithelial stem/progenitor cells in early life.

Publication Source (Journal or Book title)

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

First Page

312

Last Page

322

Share

COinS