IL-1 beta Promotes Expansion of IL-33(+) Lung Epithelial Stem Cells after Respiratory Syncytial Virus Infection during Infancy
Author ORCID Identifier
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
Vu, L. D., Phan, A. T., Hijano, D. R., Siefker, D. T., Tillman, H., & Cormier, S. A. (2022). IL-1 beta Promotes Expansion of IL-33(+) Lung Epithelial Stem Cells after Respiratory Syncytial Virus Infection during Infancy. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 66 (3), 312-322. https://doi.org/10.1165/rcmb.2021-0313OC