Antigen‐specific production of interleukin (IL)‐13 and IL‐5 cooperate to mediate IL‐4Rα‐independent airway hyperreactivity
Open Access
- 10 November 2003
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 33 (12), 3377-3385
- https://doi.org/10.1002/eji.200324178
Abstract
The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL‐13. Analyses of the receptor components employed by IL‐13 have shown that delivery of this cytokine to the airways of naive IL‐4Rα gene targeted (IL‐4Rα–/–) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL‐13‐mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin‐sensitized IL‐4Rα–/– mice and that these responses can be inhibited by the IL‐13 antagonist sIL‐13Rα2Fc. Therefore, antigen stimulation induces an IL‐13‐regulated response that is independent of IL‐4Rα. To determine the role of IL‐5 and eosinophils in the development of disease in antigen‐exposed IL‐4Rα–/– mice, pulmonary allergy was examined in mice deficient in both factors. IL‐4Rα/IL‐5–/– mice were significantly defective in their ability to produce IL‐13 and failed to develop AHR, suggesting that IL‐5 indirectly regulates AHR in allergic IL‐4Rα–/– mice by an IL‐13‐dependent mechanism. Collectively, these results demonstrate that IL‐13‐dependent processes regulating the development of AHR and T helper bias persist in the inthe lungs of allergic IL‐4Rα–/– mice.Keywords
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