A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6

J. P. Choi, Y. S. Kim, Y. M. Tae, E. J. Choi, B. S. Hong, S. G. Jeon, Y. S. Gho, Z. Zhu, Y. K. Kim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1322-1330
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume65
Issue number10
DOIs
StatePublished - Oct 1 2010

Keywords

  • IL-6
  • Th17
  • noneosinophilic asthma
  • vascular endothelial growth factor
  • virus-associated asthma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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