Functional importance of regional differences in localized gene expression of receptors for IL-13 in murine gut
Functional importance of regional differences in localized gene expression of receptors for IL-13 in murine gut
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DOI：
10.4049/jimmunol.176.1.491
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Shea-Donohue, T
中科院分区：
文献类型：
--
作者：
Morimoto, M;Morimoto, M;Shea-Donohue, T
白细胞介素 - 13（IL - 13）诱导肠道平滑肌产生一种依赖信号转导及转录激活因子6（STAT6）的高收缩性，这种作用是通过与2型白细胞介素 - 4受体（IL - 4R）中与STAT6相连的白细胞介素 - 13受体α1亚基（IL - 13Rα1）结合来介导的。IL - 13还会与不与STAT6相连的白细胞介素 - 13受体α2（IL - 13Rα2）结合，并在体内起到限制IL - 13作用的功能。在本研究中，我们评估了白细胞介素 - 13受体各组分分布的区域和细胞差异对野生型小鼠以及信号转导及转录激活因子6（STAT6）或白细胞介素 - 13受体α2（IL - 13Rα2）缺陷小鼠平滑肌功能生理调节的影响。白细胞介素 - 13（IL - 13）和白细胞介素 - 13受体α2（IL - 13Rα2）在结肠中的表达高于小肠。对特定细胞类型进行激光捕获显微切割显示，与黏膜上皮细胞中的水平相比，白细胞介素 - 13受体α2（IL - 13Rα2）在平滑肌层中的表达更高。相比之下，白细胞介素 - 13受体α1（IL - 13Rα1）在平滑肌、上皮细胞和肌间神经元中呈均匀分布。白细胞介素 - 13受体α2（IL - 13Rα2）缺陷小鼠（而非信号转导及转录激活因子6（STAT6）缺陷小鼠）的平滑肌具有显著的高收缩性，这表明白细胞介素 - 13与白细胞介素 - 13受体α2（IL - 13Rα2）结合具有生理重要性。白细胞介素 - 13受体α2（IL - 13Rα2）表达的显著差异表明肠道已经形成了复杂的机制来控制白细胞介素 - 13的生理和病理生理活动。
IL-13 induces a STAT6-dependent hypercontractility of intestinal smooth muscle that is mediated by binding to the IL-13R alpha 1 component of the type 2 IL-4R that is linked to STAT6. IL-13 also binds to the IL-13R alpha 2 that is not linked to STAT6 and functions to limit the effects of IL-13 in vivo. In this study we assessed the contributions of regional and cellular differences in the distribution of the IL-13R components to the physiological regulation of smooth muscle function in wild-type mice and mice deficient in STAT6 or IL-13R alpha 2. The expression of IL-13 and IL-13R alpha 2 was higher in colon than in small intestine. Laser capture microdissection of specific cell types revealed that the expression of IL-13R alpha 2 was higher in the smooth muscle layer compared with levels in the epithelial cells of the mucosa. In contrast, there was a uniform distribution of 11-13 alpha 1 in smooth muscle, epithelia, and myenteric neurons. The significant hypercontractility of smooth muscle in mice deficient in IL-13R alpha 2, but not in STAT6, shows the physiological importance of IL-13 binding to IL-13R alpha 2. The pronounced differences in the expression of IL-13R alpha 2 suggest that the gut has developed sophisticated mechanisms for controlling the physiological and pathophysiological activities of IL-13.