IL-4Rα on CD4+ T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates

Dahui You, Nico Marr, Jordy Saravia, Bishwas Shrestha, Greg I. Lee, Stuart E. Turvey, Frank Brombacher, De'broski R. Herbert, Stephania A. Cormier

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28 Citations (Scopus)

Abstract

RSV is the major cause of severe bronchiolitis in infants, and severe bronchiolitis as a result of RSV is associated with subsequent asthma development. A biased Th2 immune response is thought to be responsible for neonatal RSV pathogenesis; however, molecular mechanisms remain elusive. Our data demonstrate, for the first time, that IL-4Rα is up-regulated in vitro on human CD4+ T cells from cord blood following RSV stimulation and in vivo on mouse pulmonary CD4+ T cells upon reinfection of mice, initially infected as neonates. Th cell-specific deletion of Il4ra attenuated Th2 responses and abolished the immunopathophysiology upon reinfection, including airway hyper-reactivity, eosinophilia, and mucus hyperproduction in mice infected initially as neonates. These findings support a pathogenic role for IL-4Rα on Th cells following RSV reinfection of mice initially infected as neonates; more importantly, our data from human cells suggest that the same mechanism occurs in humans.

Original languageEnglish
Pages (from-to)933-942
Number of pages10
JournalJournal of Leukocyte Biology
Volume93
Issue number6
DOIs
Publication statusPublished - 1 Jun 2013

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Keywords

  • Infants
  • T helper cells
  • Viral infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

You, D., Marr, N., Saravia, J., Shrestha, B., Lee, G. I., Turvey, S. E., Brombacher, F., Herbert, D. R., & Cormier, S. A. (2013). IL-4Rα on CD4+ T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates. Journal of Leukocyte Biology, 93(6), 933-942. https://doi.org/10.1189/jlb.1012498