| First Author | Folmsbee SS | Year | 2016 |
| Journal | J Allergy Clin Immunol | Volume | 138 |
| Issue | 1 | Pages | 123-129.e2 |
| PubMed ID | 26947180 | Mgi Jnum | J:302754 |
| Mgi Id | MGI:6509698 | Doi | 10.1016/j.jaci.2015.11.037 |
| Citation | Folmsbee SS, et al. (2016) The cardiomyocyte protein alphaT-catenin contributes to asthma through regulating pulmonary vein inflammation. J Allergy Clin Immunol 138(1):123-129.e2 |
| abstractText | BACKGROUND: Recent genome-wide association studies have identified single nucleotide polymorphisms in the gene encoding the protein alphaT-catenin (CTNNA3) that correlate with both steroid-resistant atopic asthma and asthmatic exacerbations. alpha-Catenins are important mediators of cell-cell adhesion, and alphaT-catenin is predominantly expressed in cardiomyocytes. In the lung alphaT-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 alphaT-catenin in asthma pathogenesis. METHODS: We used alphaT-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 alphaT-catenin in mice largely attenuated HDM-induced airway inflammation and airway hyperresponsiveness to methacholine. Mice lacking alphaT-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 alphaT-catenin led to compensatory upregulation of alphaE-catenin, which itself has a defined anti-inflammatory function. CONCLUSION: These data mechanistically support previous clinical and genetic associations between alphaT-catenin and the development of atopic asthma and suggest that PVs might have an underappreciated role in allergic airway inflammation. |
