JEM：中科院巴斯德所肖晖研究组等发表pDC抗病毒感染研究成果

2017-05-18 佚名生物帮

近日，国际免疫学领域重要的顶级期刊、洛克菲勒大学出版社的旗舰杂志《Journal of Experimental Medicine》在线发表了中科院上海巴斯德研究所肖晖研究组的最新研究成果：“Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDC

近日，国际免疫学领域重要的顶级期刊、洛克菲勒大学出版社的旗舰杂志《Journal of Experimental Medicine》在线发表了中科院上海巴斯德研究所肖晖研究组的最新研究成果：“Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs”(表观遗传分子CXXC5在pDC中通过招募DNA去甲基化酶Tet2调节TLR7/9诱导的I型干扰素表达)。研究首次发现在浆样树突细胞(pDC)中特异表达的表观遗传分子CXXC5通过招募DNA去甲基化酶Tet2，导致Irf7基因启动子区域的CpG岛处于低甲基化状态，从而保障了pDC中IRF7高表达及其诱导大量I型干扰素，有效清除病毒感染的能力。上海巴斯德研究所博士研究生马世鑫为论文第一作者，肖晖研究员为论文通讯作者。

在病毒感染早期，pDC能够快速产生大量的I型干扰素，因此在控制病毒感染和调节天然免疫、适应性免疫反应中起重要作用。目前为止，虽然对于pDC通过TLR7/9信号激活转录因子IRF7，诱导I型干扰素表达的信号转导路径已经比较清楚，然而对于在众多的免疫细胞中为什么只有pDC特异地高表达IRF7，其中的分子机制并不清楚。

研究通过筛选发现ZF-CXXC家族的表观遗传分子CXXC5特异地高表达于pDC中，并参与调节TLR7/9和病毒诱导的I型干扰素表达。在机制方面，发现CXXC5通过其CXXC结构域与Irf7基因启动子区域的CpG岛结合，然后招募dna去甲基化酶Tet2，以降低该区域的5’-胞嘧啶甲基化水平(5’-mC)；通过重塑该区域的染色体修饰和构型，导致IRF7组成型表达。在RNA、DNA病毒感染时，CXXC5基因敲除的小鼠不能快速产生大量的I型干扰素，因此丧失了抵抗病毒感染的能力，表明CXXC5介导的表观遗传学调控机制在宿主防御中起着重要作用。

研究首次发现了表观遗传调节机制，特别是dna甲基化修饰，在调节pDC功能方面的关键作用，验证了表观遗传学机制在免疫细胞发育、分化和功能维持方面的重要作用，也为治疗病菌感染和自身免疫性疾病提供了新思路。

原始出处：

Shixin Ma， Xiaoling Wan， Zihou Deng，et al.Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs.J Exp Med. 2017 May 1

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2018-02-18 gous

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2018-04-13 xiongliangxl

#研究成果#

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2017-07-15 仁心济世

#pDC#

79 0
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2017-06-02 jyzxjiangqin

PDC抗病毒感染研究成果。

94 0
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2017-05-20 yahu

#抗病毒#

88 0
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2017-05-20 惠映实验室

这成果来得及时，学习了

95 0
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2017-05-19 daiyaozu

学习了，不错

139 0
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2017-05-19 刘煜

学习了谢谢

69 0
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2017-05-19 飛歌

学习了很有用

103 0
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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Sat May 20 01:16:00 CST 2017, time=2017-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199831, encodeId=6fd1199831ac, content=学习了，不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=139, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/icyLhIGqru6gIknBJqfuPhQkEvDREF6S2vZq3ZIpUYjdqicKVoAWaJSGoe8xNvS6o6QpmOlh2AQ7xuUpj8NiaDjJJgjbc7Xj3T6/0, createdBy=1c242047915, createdName=daiyaozu, createdTime=Fri May 19 06:34:51 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199810, encodeId=f2e7199810d4, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Fri May 19 06:01:56 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199773, encodeId=7b1b199e73b0, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:22 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199738, encodeId=77c5199e389d, content=继续关注。 , beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Fri May 19 00:02:45 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
2017-05-19 doctorJiangchao

继续关注。

76 0