Lewis Christina C, Aronow Bruce, Hutton John, Santeliz Joanna, Dienger Krista, Herman Nancy, Finkelman Fred D, Wills-Karp Marsha
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA.
J Allergy Clin Immunol. 2009 Apr;123(4):795-804.e8. doi: 10.1016/j.jaci.2009.01.003. Epub 2009 Feb 26.
Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive.
We sought to clarify the role or roles of IL-4 and IL-13 in asthma-pathogenesis.
We used DNA Affymetrix microarrays to profile pulmonary gene expression in BALB/c mice inoculated intratracheally with ragweed pollen, house dust mite, IL-4, IL-13, or both cytokines. IL-13 dependence was confirmed by comparing pulmonary gene expression in house dust mite-inoculated wild-type and IL-13 knockout mice.
A signature gene expression profile consisting of 23 genes was commonly induced by means of inoculation with house dust mite, ragweed pollen, or IL-4 plus IL-13. Although rIL-4 and rIL-13 treatment induced an overlapping set of genes, IL-4 uniquely induced 21 genes, half of which were interferon response genes and half of which were genes important in immunoregulation. IL-13 uniquely induced 8 genes, most of which encode proteins produced by epithelial cells.
IL-4 and IL-13 together account for most allergen-induced pulmonary genes. Selective IL-4 induction of IFN-gamma response genes and other genes that might negatively regulate allergic inflammation could partially explain the greater importance of IL-13 in the effector phase of allergic airway disease.
过敏性哮喘由不适当的辅助性T细胞2（T(H)2）介导的炎症引起。白细胞介素-4（IL-4）和白细胞介素-13（IL-13）均参与哮喘的发病机制，但IL-4主要驱动T(H)2诱导，而IL-13对于变应原诱导的气道高反应性和杯状细胞增生是必需且充分的。尽管这两种细胞因子共享信号成分，但它们介导过敏性哮喘反应不同阶段的分子机制仍不清楚。
我们试图阐明IL-4和IL-13在哮喘发病机制中的作用。
我们使用DNA Affymetrix微阵列分析经气管内接种豚草花粉、屋尘螨、IL-4、IL-13或两种细胞因子的BALB/c小鼠肺组织基因表达情况。通过比较接种屋尘螨的野生型和IL-13基因敲除小鼠的肺组织基因表达来证实对IL-13的依赖性。
接种屋尘螨、豚草花粉或IL-4加IL-13共同诱导出由23个基因组成的特征性基因表达谱。尽管重组IL-4（rIL-4）和重组IL-13（rIL-13）处理诱导出一组重叠基因，但IL-4独特地诱导出21个基因，其中一半是干扰素反应基因，另一半是在免疫调节中重要的基因。IL-13独特地诱导出8个基因，其中大多数编码上皮细胞产生的蛋白质。
IL-4和IL-13共同构成了大多数变应原诱导的肺组织基因。IL-4对干扰素-γ反应基因和其他可能对过敏性炎症起负调节作用的基因的选择性诱导可能部分解释了IL-13在过敏性气道疾病效应阶段更为重要的原因。
