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TNF ‐alpha is a key mediator in the development of T h2 cell response to inhaled allergens induced by a viral PAMP double‐stranded RNA
Author(s) -
Choi J.P.,
Kim Y.S.,
Kim O. Y.,
Kim Y.M.,
Jeon S. G.,
Roh T.Y.,
Park J.S.,
Gho Y. S.,
Kim Y.K.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2012.02871.x
Subject(s) - sensitization , ovalbumin , immunology , tumor necrosis factor alpha , immune system , inflammation , t cell , medicine , chemistry
Abstract Background Viral pathogen–associated molecular patterns, such as ds RNA , disrupt airway tolerance to inhaled allergens. Specifically, the T h2 and T h17 cell responses are induced by low‐dose ds RNA and the T h1‐dominant response by high‐dose ds RNA . 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 ds RNA ‐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 T h2 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 T h2 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 ds RNA is a key mediator in the development of T h2 cell response to inhaled allergens.