IL-5 exposure in utero increases lung nerve density and airway reactivity in adult offspring

Katie M. Lebold, Matthew G. Drake, Lauren B. Hales-Beck, Allison D. Fryer, David B. Jacoby

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Asthma is characterized by airway hyperreactivity and inflammation. In the lungs, parasympathetic and sensory nerves control airway tone and induce bronchoconstriction. Dysregulation of these nerves results in airway hyperreactivity. Humans with eosinophilic asthma have significantly increased sensory nerve density in airway epithelium, suggesting that type 2 cytokines and inflammatory cells promote nerve growth. Similarly, mice with congenital airway eosinophilia also have airway hyperreactivity and increased airway sensory nerve density. Here, we tested whether this occurs during development. We show that transgenic mice that overexpress IL-5, a cytokine required for eosinophil hematopoiesis, give birth to wild-type offspring that have significantly increased airway epithelial nerve density and airway hyperreactivity that persists into adulthood. These effects are caused by in utero exposure to maternal IL-5 and resulting fetal eosinophilia. Allergen exposure of these adult wildtype offspring results in severe airway hyperreactivity, leading to fatal reflex bronchoconstriction. Our results demonstrate that fetal exposure to IL-5 is a developmental origin of airway hyperreactivity, mediated by hyperinnervation of airway epithelium.

Original languageEnglish (US)
Pages (from-to)493-502
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume62
Issue number4
DOIs
StatePublished - 2020

Keywords

  • Airway hyperreactivity
  • Asthma
  • Eosinophil
  • Pregnancy
  • Sensory nerves

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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