Stat5 expression is required for IgE-mediated mast cell function
Stat5 expression is required for IgE-mediated mast cell function
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DOI：
10.4049/jimmunol.177.5.3421
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发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Ryan, John J.
中科院分区：
文献类型：
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作者：
Barnstein, Brian O.;Li, Geqiang;Ryan, John J.
现在，肥大细胞（MC）炎症反应不仅与应变，还与关节炎，多发性硬化症，心脏病和对细菌感染的抗性有关。在当前的研究中，我们证明了转录5（STAT5）的信号换能器和激活因子被IGE交叉链接迅速激活，并且其表达对MC响应至关重要。 STAT5缺陷型（Stat5KO）MC显示出IgE介导的脱粒，白细胞B，生产，细胞因子分泌和生存信号的显着降低。细胞因子产生的缺陷可能是由细胞因子mRNA稳定性降低引起的。 STAT5KO MC诱导IgE交联后通常在IgE交联后诱导的细胞因子mRNA，但是这些mRNA随着时间的流逝没有持续，并以WT细胞中观察到的速率的两倍降解。有趣的是，在STAT5KO中IgE交联后，诱导RNA不稳定的蛋白三烷二磷蛋白，但没有诱导野生型细胞。此外，通过短发蛋白RNA转染降低三磷酸表达，显着增加了STAT5KO MC的IL-13产生。我们的工作表明，STAT5是IgE诱导的MC激活的关键因素，部分通过细胞因子mRNA稳定性的转录后控制作用。这些数据直接影响与MC相关的炎症和自身免疫性疾病。
The mast cell (MC) inflammatory response is now linked not only to atopy, but also to arthritis, multiple sclerosis, heart disease, and resistance to bacterial infection. In the current study, we demonstrate that the signal transducer and activator of transcription 5 (Stat5) is rapidly activated by IgE cross-linkage, and that its expression is critical to the MC response. Stat5-deficient (Stat5KO) MC demonstrated a significant decrease in IgE-mediated degranulation, leukotriene B, production, cytokine secretion, and survival signals. The defect in cytokine production may be caused by decreased cytokine mRNA stability. Stat5KO MC-induced cytokine mRNAs normally following IgE cross-linkage, but these mRNAs were not sustained over time and were degraded at twice the rate observed in WT cells. Interestingly, the RNA destabilizing protein tristetraprolin was induced following IgE cross-linkage in Stat5KO but not wild-type cells. Moreover, reducing tristetraprolin expression via short hairpin RNA transfection significantly increased IL-13 production in Stat5KO MC. Our work demonstrates that Stat5 is a critical factor in IgE-induced MC activation, acting in part via posttranscriptional control of cytokine mRNA stability. These data have a direct impact on MC-associated inflammatory and autoimmune diseases.