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J Allergy Clin Immunol. 2007 Oct;120(4):803-12. Epub 2007 Jul 5.

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

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  • 1Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Pohang, Korea.

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-gamma-, 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-gamma-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-gamma 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 T(H)1 and T(H)2 immune responses to inhaled allergens.

CLINICAL IMPLICATIONS:

Targeting both T(H)1 and T(H)2 lung inflammation might be important in the treatment of virus-associated asthma.

PMID:
17610940
[PubMed - indexed for MEDLINE]
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