TNF-alpha is a key mediator in the development of Th2 cell response to inhaled allergens induced by a viral PAMP double-stranded RNA
| Autor: | Jun Pyo Choi, S. G. Jeon, Y.-K. Kim, Yong Song Gho, O. Y. Kim, Yu Sun Kim, Young-Min Kim, J.-S. Park, T.-Y. Roh |
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| Rok vydání: | 2012 |
| Předmět: |
Immunology
Cell Biology law.invention Mice Th2 Cells Mediator law Administration Inhalation medicine Animals Immunology and Allergy Sensitization Interleukin 4 RNA Double-Stranded Tumor Necrosis Factor-alpha Allergens respiratory system Asthma respiratory tract diseases Mice Inbred C57BL Disease Models Animal Ovalbumin medicine.anatomical_structure Recombinant DNA biology.protein RNA Viral Tumor necrosis factor alpha Bronchial Hyperreactivity Airway |
| Zdroj: | Allergy. 67:1138-1148 |
| ISSN: | 0105-4538 |
| DOI: | 10.1111/j.1398-9995.2012.02871.x |
| Popis: | Background Viral pathogen–associated molecular patterns, such as dsRNA, disrupt airway tolerance to inhaled allergens. Specifically, the Th2 and Th17 cell responses are induced by low-dose dsRNA and the Th1-dominant response by high-dose dsRNA. Objective In this model, we evaluate the role of TNF-α in the development of adaptive immune dysfunction to inhaled allergens induced by airway sensitization with dsRNA-containing allergens. Methods A virus-associated asthma mouse model was generated via simultaneous airway administration of ovalbumin (OVA) and low (0.1 μg) or high (10 μg) doses of polyinosine–polycytidylic acid (poly[I:C]). The effect of TNF-α on Th2 airway inflammation was evaluated using TNF-α-deficient mice and recombinant TNF-α. Results TNF-α production was enhanced by airway exposure to low and high doses of poly[I:C]. After airway sensitization with OVA plus low-dose poly[I:C], TNF-α-deficient mice exhibited less OVA-induced airway inflammation than did wild-type (WT) mice. However, this did not occur upon sensitization with high-dose poly[I:C]. In terms of T-cell response, the production of IL-4 from lung T cells after OVA challenge was enhanced by airway sensitization with OVA plus low-dose poly[I:C] in WT mice, and this phenotype was inhibited by the absence of TNF-α. Moreover, the Th2 cell response induced by sensitization with OVA plus low-dose poly[I:C], which was abolished in TNF-α-deficient mice, was restored in these mice upon addition of recombinant TNF-α. Conclusion The results of this study suggest that TNF-α produced by airway exposure to low-dose dsRNA is a key mediator in the development of Th2 cell response to inhaled allergens. |
| Databáze: | OpenAIRE |
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