Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
J Allergy Clin Immunol. 2013 Oct;132(4):951-8.e1-6. doi: 10.1016/j.jaci.2013.04.016. Epub 2013 Jun 12.
IL-13 receptor α2 (IL-13Rα2) binds IL-13 with high affinity and modulates IL-13 responses. There are soluble and membrane forms of IL-13Rα2 generated by alternative splicing in mice, but human subjects express only the membrane form of IL-13Rα2 (memIL-13Rα2).
We determined the role of memIL-13Rα2 in the development of allergic inflammation in mouse models of asthma.
IL-13Rα2-deficient and memIL-13Rα2 lung epithelium-specific transgenic mice were challenged with house dust mite (HDM). Airway hyperresponsiveness (AHR) and inflammation were assessed based on the airway pressure-time index, bronchoalveolar lavage (BAL) cell counts, and lung histology. Mucus production was determined by means of periodic acid-Schiff staining of lung sections, Western blot analysis of chloride channel calcium activated 3 (CLCA3) expression in lung homogenates, and ELISA of Muc5ac in BAL fluid. The expression of cytokines and chemokines was determined by using RT-quantitative PCR.
In IL-13Rα2-deficient mice AHR and airway inflammation were attenuated compared with levels seen in wild-type mice after HDM challenge. Lung epithelial overexpression of memIL-13Rα2 in the IL-13Rα2-deficient mice reconstituted AHR and inflammation to levels similar to those observed in HDM-challenged wild-type mice. Mucus production was attenuated in lungs from HDM-treated IL-13Rα2-deficient mice, whereas lung epithelial overexpression of memIL-13Rα2 increased mucus production. Lung epithelial overexpression of memIL-13Rα2 had no effect on levels of the soluble form of IL-13Rα2 in serum or BAL fluid and did not affect IL-13-dependent signal transducer and activator of transcription 6 activation in the lungs.
These data collectively support a distinct role for memIL-13Rα2 in the lung and suggest that memIL-13Rα2 might contribute to allergic inflammation.
白细胞介素 13 受体 α2（IL-13Rα2）与白细胞介素 13（IL-13）具有高亲和力结合，并调节 IL-13 反应。在小鼠中，IL-13Rα2 通过选择性剪接产生可溶性和膜形式，但人体仅表达 IL-13Rα2 的膜形式（memIL-13Rα2）。
我们确定了 memIL-13Rα2 在哮喘小鼠模型中过敏性炎症发展中的作用。
用屋尘螨（HDM）对 IL-13Rα2 缺陷和 memIL-13Rα2 肺上皮特异性转基因小鼠进行挑战。根据气道压力-时间指数、支气管肺泡灌洗（BAL）细胞计数和肺组织学评估气道高反应性（AHR）和炎症。通过肺切片过碘酸希夫染色、肺匀浆氯离子通道钙激活 3（CLCA3）表达的 Western blot 分析和 BAL 液中 Muc5ac 的 ELISA 测定来确定粘液产生。通过 RT-定量 PCR 测定细胞因子和趋化因子的表达。
与 HDM 挑战后野生型小鼠相比，IL-13Rα2 缺陷型小鼠 AHR 和气道炎症减弱。在 IL-13Rα2 缺陷型小鼠中肺上皮过表达 memIL-13Rα2，使 AHR 和炎症恢复到与 HDM 处理的野生型小鼠相似的水平。与 HDM 处理的 IL-13Rα2 缺陷型小鼠相比，肺部粘液产生减少，而肺上皮过表达 memIL-13Rα2 增加了粘液产生。肺上皮过表达 memIL-13Rα2 对血清或 BAL 液中可溶性 IL-13Rα2 的水平没有影响，也不影响肺中 IL-13 依赖性信号转导和转录激活因子 6 的激活。
这些数据共同支持 memIL-13Rα2 在肺部的独特作用，并表明 memIL-13Rα2 可能有助于过敏性炎症。
