E3 泛素连接酶衔接蛋白 Ndfip1 通过限制促炎细胞因子的产生来调节 Th17 分化。
The E3 ubiquitin ligase adaptor Ndfip1 regulates Th17 differentiation by limiting the production of proinflammatory cytokines.
机构信息
School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
J Immunol. 2012 Apr 15;188(8):4023-31. doi: 10.4049/jimmunol.1102779. Epub 2012 Mar 7.
Abstract
Ndfip1 is an adaptor for the E3 ubiquitin ligase Itch. Both Ndfip1- and Itch-deficient T cells are biased toward Th2 cytokine production. In this study, we demonstrate that lungs from Ndfip1(-/-) mice showed increased numbers of neutrophils and Th17 cells. This was not because Ndfip1(-/-) T cells are biased toward Th17 differentiation. In fact, fewer Ndfip1(-/-) T cells differentiated into Th17 cells in vitro due to high IL-4 production. Rather, Th17 differentiation was increased in Ndfip1(-/-) mice due to increased numbers of IL-6-producing eosinophils. IL-6 levels in mice that lacked both Ndfip1 and IL-4 were similar to wild-type controls, and these mice had fewer Th17 cells in their lungs. These results indicate that Th2 inflammation, such as that observed in Ndfip1(-/-) mice, can increase Th17 differentiation by recruiting IL-6-producing eosinophils into secondary lymphoid organs and tissues. This may explain why Th17 cells develop within an ongoing Th2 inflammatory response.
摘要
Ndfip1 是 E3 泛素连接酶 Itch 的衔接蛋白。Ndfip1 和 Itch 缺陷的 T 细胞偏向于产生 Th2 细胞因子。在这项研究中，我们证明 Ndfip1(-/-) 小鼠的肺部有更多的中性粒细胞和 Th17 细胞。这并不是因为 Ndfip1(-/-) T 细胞偏向于 Th17 分化。事实上，由于高水平的 IL-4 产生，体外 Ndfip1(-/-) T 细胞分化为 Th17 细胞的数量较少。相反，由于产生 IL-6 的嗜酸性粒细胞数量增加，Ndfip1(-/-) 小鼠的 Th17 分化增加。缺乏 Ndfip1 和 IL-4 的小鼠的 IL-6 水平与野生型对照相似，并且它们的肺部 Th17 细胞较少。这些结果表明，Th2 炎症（如 Ndfip1(-/-) 小鼠中观察到的炎症）可以通过将产生 IL-6 的嗜酸性粒细胞募集到次级淋巴器官和组织中来增加 Th17 分化。这可能解释了为什么 Th17 细胞在持续的 Th2 炎症反应中发展。
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本文引用的文献
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