TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA

Seong Gyu Jeon, Sun Young Oh, Hye Kyung Park, You Sun Kim, Eun Jin Shim, Hyun Seung Lee, Min Hee Oh, Boram Bang, Eun Young Chun, Sang Heon Kim, Yong Song Gho, Zhou Zhu, You Young Kim, Yoon Keun Kim

Research output: Contribution to journalArticle

Abstract

Background: Although respiratory viral infections in early childhood can enhance the development of airway allergen sensitization, the exact mechanisms of the effects of viral infections on the adaptive immune response to inhaled allergens are controversial. Objective: We sought to evaluate the effects of double-stranded RNA (dsRNA) on airway sensitization to inhaled allergens. Methods: Novel mouse models were created through simultaneous airway sensitization to an allergen and low or high doses of dsRNA. The mouse models were applied to Toll-like receptor 3-, IL-13-, IL-4-, signal transducer and activator of transcription (STAT) 6-, IFN-γ-, and T-box expressed in T cells (T-bet)-deficient mice to evaluate underlying pathophysiologic mechanisms in the development of allergic lung inflammation. Results: We found that airway allergen sensitization with dsRNA induced lung inflammation that was not present in Toll-like receptor 3-deficient mice. Moreover, lung inflammation enhanced by low-dose dsRNA was impaired in IL-13-deficient mice, whereas lung inflammation by high-dose dsRNA was impaired in IFN-γ-deficient mice. The models also demonstrated that low-dose dsRNA enhanced IL-4 expression during allergen sensitization and that inflammation enhanced by low-dose dsRNA was not present in IL-4- or STAT6-deficient mice. In contrast, the present study showed that high-dose dsRNA enhanced IFN-γ expression during allergen sensitization and that the development of lung inflammation enhanced by high-dose dsRNA was impaired in T-bet-deficient mice. Conclusion: These findings suggest that airway allergen exposure during respiratory viral infections might induce asthma induced by both TH1 and TH2 immune responses to inhaled allergens. Clinical implications: Targeting both TH1 and TH2 lung inflammation might be important in the treatment of virus-associated asthma.

Original languageEnglish (US)
Pages (from-to)803-812
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number4
DOIs
StatePublished - Oct 2007

Keywords

  • Double-stranded RNA
  • T1
  • T2
  • allergic inflammation
  • virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Jeon, S. G., Oh, S. Y., Park, H. K., Kim, Y. S., Shim, E. J., Lee, H. S., Oh, M. H., Bang, B., Chun, E. Y., Kim, S. H., Gho, Y. S., Zhu, Z., Kim, Y. Y., & Kim, Y. K. (2007). TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA. Journal of Allergy and Clinical Immunology, 120(4), 803-812. https://doi.org/10.1016/j.jaci.2007.05.030