Kuperman D, Schofield B, Wills-Karp M, Grusby M J
Department of Environmental Health Sciences, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA.
J Exp Med. 1998 Mar 16;187(6):939-48. doi: 10.1084/jem.187.6.939.
The pleiotropic cytokine interleukin 4 (IL-4) has been shown to regulate many processes thought to be important in the allergic diathesis. To determine the mechanism(s) by which IL-4 mediates allergic airway responses to inhaled allergens, we compared the effects of antigen sensitization and challenge on the development of allergic airway responses in mice in which the gene for the signal transducer and activator of transcription factor 6 (Stat6) was disrupted to those of their wild-type littermates. Strikingly, Stat6-deficient mice failed to develop airway hyperresponsiveness (AHR), which was observed in their wild-type littermates after allergen provocation. Moreover, antigen-induced increases in mucus-containing cells were found to be completely Stat6 dependent. Consistent with the lack of Th2 cytokine responses in Stat6-deficient mice, no ovalbumin-specific immunoglobulin (Ig)E was detected in their serum. In contrast, Stat6 signaling only partially mediated antigen-induced eosinophilia with no role in vascular adhesion molecule 1 expression. These results indicate that Stat6 signal transduction is critical in the development of allergen-induced AHR and that agents that specifically inhibit this pathway may provide a novel strategy for the treatment of allergic disorders.
多效性细胞因子白细胞介素4（IL-4）已被证明可调节许多在过敏性素质中被认为很重要的过程。为了确定IL-4介导对吸入变应原的过敏性气道反应的机制，我们比较了抗原致敏和激发对信号转导及转录激活因子6（Stat6）基因被破坏的小鼠与它们野生型同窝小鼠过敏性气道反应发展的影响。令人惊讶的是，Stat6缺陷小鼠未能出现气道高反应性（AHR），而其野生型同窝小鼠在变应原激发后出现了这种情况。此外，发现抗原诱导的含黏液细胞增加完全依赖于Stat6。与Stat6缺陷小鼠缺乏Th2细胞因子反应一致，在它们的血清中未检测到卵清蛋白特异性免疫球蛋白（Ig）E。相反，Stat6信号传导仅部分介导抗原诱导的嗜酸性粒细胞增多，对血管黏附分子1的表达没有作用。这些结果表明，Stat6信号转导在变应原诱导的AHR发展中至关重要，特异性抑制该途径的药物可能为治疗过敏性疾病提供一种新策略。
