Ets-1 is a negative regulator of Th17 differentiation.
Ets-1 is a negative regulator of Th17 differentiation.
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DOI：
10.1084/jem.20070994
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发表时间：
2007-11-26
影响因子：
15.3
通讯作者：
Ho, I-Cheng
中科院分区：
文献类型：
--
作者：
Moisan, Jacques;Grenningloh, Roland;Bettelli, Estelle;Oukka, Mohamed;Ho, I-Cheng
IL-17是一种促炎细胞因子，其在细胞外细菌的清除中起作用，并促成许多自身免疫性和过敏性病症的病理学。IL-17主要由新表征的称为Th 17的T辅助（Th）细胞亚群产生。虽然Th 17细胞在自身免疫性疾病的病理学中的作用已经得到很好的确立，但是调节Th 17细胞分化的转录因子仍然缺乏表征。我们报告说，Ets-1缺陷型Th细胞比野生型细胞更有效地分化为Th 17细胞。这归因于低IL-2产生和对IL-2对Th 17分化的抑制作用的抗性增加。对IL-2抑制的抵抗是由STAT 5磷酸化下游的缺陷引起的，但不是由RORγt水平的差异引起的。此外，Ets-1缺陷小鼠的肺中含有异常高水平的IL-17转录物，并表现出气道上皮细胞以IL-17依赖的方式增加粘液产生。基于这些观察，我们报告说，Ets-1是一个负调节Th 17分化。
IL-17 is a proinflammatory cytokine that plays a role in the clearance of extracellular bacteria and contributes to the pathology of many autoimmune and allergic conditions. IL-17 is produced mainly by a newly characterized subset of T helper (Th) cells termed Th17. Although the role of Th17 cells in the pathology of autoimmune diseases is well established, the transcription factors regulating the differentiation of Th17 cells remain poorly characterized. We report that Ets-1–deficient Th cells differentiated more efficiently to Th17 cells than wild-type cells. This was attributed to both low IL-2 production and increased resistance to the inhibitory effect of IL-2 on Th17 differentiation. The resistance to IL-2 suppression was caused by a defect downstream of STAT5 phosphorylation, but was not caused by a difference in the level of RORγt. Furthermore, Ets-1–deficient mice contained an abnormally high level of IL-17 transcripts in their lungs and exhibited increased mucus production by airway epithelial cells in an IL-17–dependent manner. Based on these observations, we report that Ets-1 is a negative regulator of Th17 differentiation.
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