IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction

Nat Med. 2012 Mar 4;18(4):547-54. doi: 10.1038/nm.2684.


Emerging evidence suggests that the T helper 17 (T(H)17) subset of αβ T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the αvβ8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin αvβ8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Asthma / immunology
  • Asthma / pathology*
  • CD11c Antigen / genetics
  • CD4 Antigens
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Humans
  • In Vitro Techniques
  • Integrin alphaV / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-17 / pharmacology*
  • Male
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscarinic Agonists / pharmacology
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology
  • Muscle, Smooth / drug effects*
  • Ovalbumin / immunology
  • Potassium Chloride / pharmacology
  • Respiratory System / cytology
  • Signal Transduction / drug effects
  • Th17 Cells / metabolism*
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism


  • CD11c Antigen
  • CD4 Antigens
  • Enzyme Inhibitors
  • Integrin alphaV
  • Interleukin-17
  • Muscarinic Agonists
  • Methacholine Chloride
  • Potassium Chloride
  • Ovalbumin
  • ROCK1 protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein