Edited by: Hans-Uwe Simon
A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6
Article first published online: 23 APR 2010
© 2010 John Wiley & Sons A/S
Volume 65, Issue 10, pages 1322–1330, October 2010
How to Cite
Choi, J.-P., Kim, Y.-S., Tae, Y.-M., Choi, E.-J., Hong, B.-S., Jeon, S. G., Gho, Y. S., Zhu, Z. and Kim, Y.-K. (2010), A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6. Allergy, 65: 1322–1330. doi: 10.1111/j.1398-9995.2010.02369.x
- Issue published online: 7 SEP 2010
- Article first published online: 23 APR 2010
- Accepted for publication 16 February 2010
- noneosinophilic asthma;
- vascular endothelial growth factor;
- virus-associated asthma
To cite this article: Choi J-P, Kim Y-S, Tae Y-M, Choi E-J, Hong B-S, Jeon SG, Gho YS, Zhu Z, Kim Y-K. A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6. Allergy 2010; 65: 1322–1330.
Background: Innate immune response by a viral pathogen-associated molecular pattern dsRNA modulates the subsequent development of adaptive immune responses. Although virus-associated asthma is characterized by noneosinophilic inflammation, the role of Th17 cell response in the development of virus-associated asthma is still unknown.
Objective: To evaluate the role of the Th17 cell response and its underlying polarizing mechanisms in the development of an experimental virus-associated asthma.
Methods: An experimental virus-associated asthma was created via airway sensitization with ovalbumin (OVA, 75 μg) and a low (0.1 μg) or a high (10 μg) doses of synthetic dsRNA [polyinosine–polycytidylic acid; poly(I:C)]. Transgenic (IL-17-, IL-6-deficient mice) and pharmacologic [a vascular endothelial growth factor receptor (VEGFR) inhibitor] approaches were used to evaluate the roles of Th17 cell responses.
Results: After cosensitization with OVA and low-dose poly(I:C), but not with high-dose poly(I:C), inflammation scores after allergen challenge were lower in IL-17-deficient mice than in wild-type (WT) mice. Moreover, inflammation enhanced by low-dose poly(I:C), but not by high-dose poly(I:C), was impaired in IL-6-deficient mice; this phenotype was accompanied by the down-regulation of IL-17 production from T cells from both lymph nodes and lung tissues. Airway exposure of low-dose poly(I:C) enhanced the production of VEGF and IL-6, and the production of IL-6 was blocked by treatment with a VEGFR inhibitor (SU5416). Moreover, the allergen-specific Th17 cell response and subsequent inflammation in the low-dose poly(I:C) model were impaired by the VEGFR inhibitor treatment during sensitization.
Conclusions: Airway exposure of low-level dsRNA induces an allergen-specific Th17 cell response, which is mainly dependent on VEGF and IL-6.