Integrins α v 5 and avb6 mediate IL-4-induced collective migration in human airway epithelial cells

Sang Nam Lee, Ji Suk Ahn, Seong Gyu Lee, Hyung Suk Lee, Augustine M.K. Choi, Joo Heon Yoon

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13 Citations (Scopus)


A positive link between persistent cellular motion and a defective tight junction barrier allows increased antigenic penetration and contact between ligand-receptor pairs, leading to exacerbated allergic airway inflammation and remodeling. Given that collective cell migration involves cell-cell and cell-extracellular matrix adhesions, and given that IL-4 induces epithelial barrier dysfunction and decreases cell-extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelial cells (HNECs). Well-differentiated HNECs were treated with IL-4, and the effects of IL-4 on cell migration were investigated using genetic and pharmacological approaches, live-cell imaging, a vertex model, and immunostaining. IL-4 disrupted the expression and localization of the tight junction proteins zonula occludens 1 and occludin, and it induced the cleavage and asymmetric distribution of E-cadherin in the HNEC layers. It also induced collective epithelial migration and cell shape changes driven by actin cytoskeleton reorganization. In addition, the effect of IL-4 on collective HNEC migration was reversed by pharmacologic and genetic inhibition of the av-integrin-activating enzyme furin, and function-blocking antibodies for α v 5 or avb6. In IL-4-stimulated cells, both anti-α v 5 and anti-avb6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both b5-and b6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that α v 5 and a vb6 serve as critical mechanoreceptors in IL-4-induced collective HNEC migration through the focal adhesion kinase signaling pathway. These results have implications for targeting treatment of exacerbation of respiratory allergic diseases.

Original languageEnglish
Pages (from-to)420-433
Number of pages14
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number4
Publication statusPublished - 2019 Apr

Bibliographical note

Funding Information:
Supported by Global Research Laboratory (GRL) Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (2016K1A1A2910779 [J.-H.Y. and A.M.K.C.]), and by the Basic Science Research Program through the NRF, funded by the Ministry of Education (2016R1D1A1B01007747 [S.-N.L.]).

Publisher Copyright:
© 2019 by the American Thoracic Society.

All Science Journal Classification (ASJC) codes

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


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