Unique Allergic Asthma Phenotypes in Offspring of House Dust Mite-exposed Mice

Katie M. Lebold, Matthew Drake, Alexandra B. Pincus, Aubrey B. Pierce, Allison Fryer, David B. Jacoby

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Asthma is a heterogeneous inflammatory airway disease that develops in response to a combination of genetic predisposition and environmental exposures. Patients with asthma are grouped into phenotypes with shared clinical features and biomarker profiles to help tailor specific therapies. However, factors driving development of specific phenotypes are poorly understood. Prenatal exposure to maternal asthma is a unique risk factor for childhood asthma. Here we tested whether maternal asthma skews asthma phenotypes in offspring. We compared airway hyperreactivity and inflammatory and neurotrophin lung signatures before and after allergen challenge in offspring born to mice exposed to house dust mite (HDM) or vehicle during pregnancy. Maternal HDM exposure potentiated offspring responses to HDM allergen, significantly increasing both airway hyperreactivity and airway eosinophilia compared with control mice. Maternal HDM exposure broadly skewed the offspring cytokine response from a classic allergen-induced T-helper cell type 2 (Th2)-predominant signature in HDM-treated offspring of vehicle-exposed mothers, toward a mixed Th17/Th1 phenotype in HDM-treated offspring of HDM-exposed mothers. Morphologic analysis determined that maternal HDM exposure also increased airway epithelial sensory nerve density and induced distinct neurotrophin signatures to support airway hyperinnervation. Our results demonstrate that maternal allergen exposure alters fetal lung development and promotes a unique inflammatory phenotype at baseline and in response to allergen that persists into adulthood.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume67
Issue number1
DOIs
StatePublished - Jul 2022

Keywords

  • airway hyperreactivity
  • asthma
  • eosinophil
  • maternal asthma
  • sensory nerve

ASJC Scopus subject areas

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

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