曹雪涛院士Nature发文阐述免疫调控新机制

2015-08-26 佚名 生物谷

                                               近日,来自中国第二军医大学的曹雪涛院士研究小组在著名国际学术期

                                            
近日,来自中国第二军医大学的曹雪涛院士研究小组在著名国际学术期刊nature上发表了一项最新研究进展,他们发现DNA修饰酶Tet2能够在炎症过程中抑制IL-6的转录表达,并且这种作用不依赖Tet2的DNA修饰功能,通过DNA修饰非依赖性方式在炎症消退过程中发挥重要的抑制性作用。

表观遗传学修饰能够通过建立和维持谱系特异性的染色质和甲基化水平,在决定细胞命运方面发挥非常重要的作用。几种DNA修饰如5羟甲基胞嘧啶(5hmC)都是通过Tet家族成员进行催化形成的,近年来一些研究逐步发现Tet家族成员在调节染色质结构和基因转录方面发挥重要功能。但在不依赖DNA甲基化调节功能的情况下,Tet家族能否调节免疫和炎症过程仍未可知。

在这项最新研究中,研究人员发现Tet2能够在炎症过程中选择性介导对先天髓细胞中IL-6的转录抑制,缺失Tet2能够导致几种炎症介导因子的表达上调,而这一过程主要发生在脂多糖刺激情况下免疫应答的晚期阶段。

研究人员利用Tet2缺失小鼠进行研究发现这种小鼠对内毒素休克和硫酸葡聚糖钠盐诱导的大肠炎的易感性更强,表现出更加严重的炎症表型,同时与野生型小鼠相比,IL-6的合成也会增加。

通过对机制进行研究,研究人员发现IL-6特异性的转录因子IkBζ介导了Tet2对IL6启动子的特异性靶向调节,进一步提示IkBζ可能在炎症起始阶段和消退阶段发挥着相反的调控作用。而Tet2对炎症的抑制作用不依赖于DNA甲基化和羟甲基化,它能够招募Hdac2调节组蛋白的乙酰化修饰水平,达到抑制IL-6 转录的目的。

这项研究对Tet2的基因特异性转录抑制活性进行了深入探究,发现了Tet2在免疫应答和炎症过程中发挥的重要作用,对于如何调节疾病中的炎症应答具有重要提示意义。

原文出处:

Qian Zhang,Kai Zhao.et al.Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6.science.2015



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    2016-06-19 liye789132251
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    2015-08-28 skqweasd

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