Level of expression of IL-13Rα2 impacts receptor distribution and IL-13 signaling
Level of expression of IL-13Rα2 impacts receptor distribution and IL-13 signaling
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DOI：
10.4049/jimmunol.176.12.7495
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Hershey, Gurjit K. Khurana
中科院分区：
文献类型：
--
作者：
Daines, Michael O.;Tabata, Yasuhiro;Hershey, Gurjit K. Khurana
IL-13是过敏性炎症的关键细胞因子，通过包括IL-4 R α、IL-13 R α 1和IL-13 R α 2在内的复杂受体系统发挥其作用。IL-4 Ra和IL-13 Ra 1形成IL-13的异二聚体信号传导受体。相比之下，IL-13 Ra 2以高亲和力结合IL-13但不发信号。IL-13 R α 2存在于细胞表面、细胞内和以可溶性形式存在，但没有关于IL-13 R α 2在这些区室中的相对分布、区室是否连通以及相对表达水平如何影响IL-13应答的信息。在此，我们研究了IL-13 R α 2在转染细胞和原代细胞中的分布，并且我们评估了IL-13 R α 2表达的总水平如何影响其分布。我们的研究结果表明，IL-13 R α 2的分布是独立的整体表达水平。大部分IL-13 R α 2蛋白存在于细胞内池中。表面IL-13 R α 2以可溶形式持续释放到培养基中，而表面表达保持恒定，支持受体运输到细胞表面。IL-13 Ra 2抑制IL-13信号传导与其表达水平成比例，并且这种抑制可以用高浓度的IL-13克服。
IL-13, a critical cytokine for allergic inflammation, exerts its effects through a complex receptor system including IL-4R alpha, IL-13R alpha 1, and IL-13R alpha 2. IL-4R alpha and IL-13R alpha 1 form a heterodimeric signaling receptor for IL-13. In contrast, IL-13Ra2 binds IL-13 with high affinity but does not signal. IL-13R alpha 2 exists on the cell surface, intracellularly, and in soluble form, but no information is available regarding the relative distributions of IL-13R alpha 2 among these compartments, whether the compartments communicate, and how the relative expression levels impact IL-13 responses. Herein, we investigated the distribution of IL-13R alpha 2 in transfected and primary cells, and we evaluated how the total level of IL-13Ra2 expression impacted its distribution. Our results demonstrate that the distribution of IL-13R alpha 2 is independent of the overall level of expression. The majority of the IL-13R alpha 2 protein existed in intracellular pools. Surface IL-13R alpha 2 was continually released into the medium in a soluble form, yet surface expression remained constant supporting receptor trafficking to the cell surface. IL-13Ra2 inhibited IL-13 signaling proportionally to its level of expression, and this inhibition could be overcome with high concentrations of IL-13.