The cardiomyocyte protein αT-catenin contributes to asthma through regulating pulmonary vein inflammation

Stephen Sai Folmsbee, G. R.Scott Budinger, Paul J. Bryce, Cara J. Gottardi*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background Recent genome-wide association studies have identified single nucleotide polymorphisms in the gene encoding the protein αT-catenin (CTNNA3) that correlate with both steroid-resistant atopic asthma and asthmatic exacerbations. α-Catenins are important mediators of cell-cell adhesion, and αT-catenin is predominantly expressed in cardiomyocytes. In the lung αT-catenin appears to be exclusively expressed in cardiomyocytes surrounding the pulmonary veins (PVs), but its contribution to atopic asthma remains unknown. Objective We sought to understand the role of αT-catenin in asthma pathogenesis. Methods We used αT-catenin knockout mice and a house dust mite (HDM) extract model of atopic asthma, with assessment by means of forced oscillation, bronchoalveolar lavage, and histologic analysis. Results We found that the genetic loss of αT-catenin in mice largely attenuated HDM-induced airway inflammation and airway hyperresponsiveness to methacholine. Mice lacking αT-catenin that were exposed to HDM extract had reduced PV inflammation, specifically near the large veins surrounded by cardiac cells. The proximity of the airways to PVs correlated with the severity of airway goblet cell metaplasia, suggesting that PVs can influence the inflammatory milieu of adjacent airways. Loss of αT-catenin led to compensatory upregulation of αE-catenin, which itself has a defined anti-inflammatory function. Conclusion These data mechanistically support previous clinical and genetic associations between αT-catenin and the development of atopic asthma and suggest that PVs might have an underappreciated role in allergic airway inflammation.

Original languageEnglish (US)
Pages (from-to)123-129.e2
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number1
DOIs
StatePublished - Jul 1 2016

Keywords

  • CTNNA3
  • cardiomyocyte
  • cell-cell adhesion
  • pulmonary vein
  • αT-catenin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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