Nascent endothelium initiates Th2 polarization of asthma

Research output: Contribution to journalArticle


  • Kewal Asosingh
  • Georgiana Cheng
  • Weiling Xu
  • Benjamin M. Savasky
  • Mark A. Aronica
  • Xiaoxia Li
  • Serpil C. Erzurum

External Institution(s)

  • Cleveland Clinic Foundation


Original languageEnglish (US)
Pages (from-to)3458-3465
Number of pages8
JournalJournal of Immunology
Issue number7
StatusPublished - Apr 1 2013


Asthma airway remodeling is linked to Th2 inflammation. Angiogenesis is a consistent feature of airway remodeling, but its contribution to pathophysiology remains unclear.We hypothesized that nascent endothelial cells in newly forming vessels are sufficient to initiate Th2-inflammation. Vascular endothelial (VE)-cadherin is a constitutively expressed endothelial cell adhesion molecule that is exposed in its monomer form on endothelial tip cells prior to adherens junction formation. Abs targeted to VE-cadherin monomers inhibit angiogenesis by blocking this adherens junction formation. In this study, VE-cadherin monomer Ab reduced angiogenesis in the lungs of the allergen-induced murine asthma model. Strikingly, Th2 responses including, IgE production, eosinophil infiltration of the airway, subepithelial fibrosis, mucus metaplasia, and airway-hyperreactivity were also attenuated by VE-cadherin blockade, via mechanisms that blunted endothelial IL-25 and proangiogenic progenitor cell thymic stromal lymphopoietin production. The results identify angiogenic responses in the origins of atopic inflammation. Copyright

Citation formats


Asosingh, K., Cheng, G., Xu, W., Savasky, B. M., Aronica, M. A., Li, X., & Erzurum, S. C. (2013). Nascent endothelium initiates Th2 polarization of asthma. Journal of Immunology, 190(7), 3458-3465.


Asosingh, K, Cheng, G, Xu, W, Savasky, BM, Aronica, MA, Li, X & Erzurum, SC 2013, 'Nascent endothelium initiates Th2 polarization of asthma', Journal of Immunology, vol. 190, no. 7, pp. 3458-3465.