IL-5 Exposure In Utero Increases Lung Nerve Density and Airway Reactivity in Adult Offspring

Am J Respir Cell Mol Biol. 2020 Apr;62(4):493-502. doi: 10.1165/rcmb.2019-0214OC.


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 wild-type 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.

Keywords: airway hyperreactivity; asthma; eosinophil; pregnancy; sensory nerves.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Asthma / metabolism
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / metabolism
  • Bronchial Hyperreactivity / physiopathology
  • Bronchoalveolar Lavage Fluid
  • Bronchoconstriction / physiology
  • Eosinophils / metabolism
  • Eosinophils / physiology
  • Female
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Interleukin-5 / metabolism*
  • Lung / innervation*
  • Lung / metabolism*
  • Lung / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pulmonary Eosinophilia / metabolism
  • Pulmonary Eosinophilia / physiopathology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / physiology
  • Vagus Nerve / metabolism*
  • Vagus Nerve / physiology*


  • Interleukin-5