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Blood:Delta样4介导Notch信号调控慢性移植物抗宿主病的发生

2018-09-05 MedSci MedSci原创

中心点:在骨髓移植的小鼠模型中,Notch信号驱动慢性移植物抗宿主病的发生。封闭Notch配体和(或)受体可预防或治疗小鼠不同形式的慢性移植物抗宿主病。摘要:慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植(allo-HCT)的一种主要并发症,目前可供选择的治疗方案很少,尚不能满足临床需要。在多种小鼠模型中,封闭Notch可预防急性GVHD,但Notch信号对cGVHD的影响尚不明确。Ved

中心点:

在骨髓移植的小鼠模型中,Notch信号驱动慢性移植物抗宿主病的发生。

封闭Notch配体和(或)受体可预防或治疗小鼠不同形式的慢性移植物抗宿主病。

摘要:

慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植(allo-HCT)的一种主要并发症,目前可供选择的治疗方案很少,尚不能满足临床需要。在多种小鼠模型中,封闭Notch可预防急性GVHD,但Notch信号对cGVHD的影响尚不明确。

Vedran Radojcic等人采用基因和抗体介导的Notch抑制策略研究Notch信号在cGVHD小鼠模型中的作用,以寻找候选治疗方法。

在硬皮病cGVHD的B10.D2→BALB/c模型中,δ样4(Dll4)驱动的Notch信号对病程进展至关重要。早期预防性的应用抗体抑制Dll4可获得最大的预防效果,而抗Delta样1(Dll1)可增强早期保护作用。

Notch缺陷型同种异体抗原特异性T细胞在增殖早期或辅助细胞极化方面未见异常,但细胞因子分泌显着降低、FoxP3+调节T细胞积累增多。在有多器官系统cGVHD和明显闭塞性细支气管炎(BO),但无皮肤硬皮症的B6→B10.BR MHC错配模型中,T细胞Notch信号缺失可提供持久的疾病防护,即使在疾病发生时,也可通过系统靶向Dll1、Dll4或两种Notch配体进行复制。

抑制Notch可减轻靶向器官损伤和生发中心形成。而且,失活T细胞的Notch1和(或)Notch2时,可观察到BO-cGVHD减轻。单纯靶向Notch2安全,且有治疗价值。

总而言之,Notch配体和受体调控cGVHD的关键致病步骤,可作为新的药物靶点用于预防或治疗不同形式的cGVHD。

原始出处:

Vedran Radojcic,et al. Notch signaling mediated by Delta-like1/4 ligands controls the pathogenesis of chronic graft-versus-host disease in mice. Blood  2018  :blood-2018-03-841155;  doi: https://doi.org/10.1182/blood-2018-03-841155

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    2019-08-22 xuyong535
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[GetPortalCommentsPageByObjectIdResponse(id=2068314, encodeId=ee0b206831427, content=<a href='/topic/show?id=90b8129e7bd' target=_blank style='color:#2F92EE;'>#Notch信号#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12977, encryptionId=90b8129e7bd, topicName=Notch信号)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Tue Aug 06 22:46:00 CST 2019, time=2019-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1745296, encodeId=c7741e4529666, content=<a href='/topic/show?id=bdc262694bb' target=_blank style='color:#2F92EE;'>#植物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62694, encryptionId=bdc262694bb, topicName=植物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6a5e35527958, createdName=xuyong535, createdTime=Thu Aug 22 04:46:00 CST 2019, time=2019-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2025341, encodeId=3ff3202534164, content=<a href='/topic/show?id=4b5958411d' target=_blank style='color:#2F92EE;'>#Delta样4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5841, encryptionId=4b5958411d, topicName=Delta样4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Fri Jul 05 11:46:00 CST 2019, time=2019-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373772, encodeId=eafd13e3772bb, content=<a href='/topic/show?id=eb3b129e01d' target=_blank style='color:#2F92EE;'>#Notch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12970, encryptionId=eb3b129e01d, topicName=Notch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ece5364, createdName=karmond, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1404714, encodeId=373c1404e1403, content=<a href='/topic/show?id=1a4f4649925' target=_blank style='color:#2F92EE;'>#宿主#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46499, encryptionId=1a4f4649925, topicName=宿主)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/08904ED76550A0090DB220A7FB81D755/100, createdBy=78512492586, createdName=wincls, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1419720, encodeId=5f721419e2067, content=<a 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time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578847, encodeId=821c15e8847f5, content=<a href='/topic/show?id=7e74536097a' target=_blank style='color:#2F92EE;'>#慢性移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53609, encryptionId=7e74536097a, topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620722, encodeId=55721620e22a4, content=<a href='/topic/show?id=c0c9e520310' target=_blank style='color:#2F92EE;'>#移植物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75203, encryptionId=c0c9e520310, topicName=移植物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=153620156575, createdName=10518100zz, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342922, encodeId=4507342922c9, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed Sep 05 19:06:57 CST 2018, time=2018-09-05, status=1, ipAttribution=)]
    2018-09-07 karmond
  5. 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time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578847, encodeId=821c15e8847f5, content=<a href='/topic/show?id=7e74536097a' target=_blank style='color:#2F92EE;'>#慢性移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53609, encryptionId=7e74536097a, topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620722, encodeId=55721620e22a4, content=<a href='/topic/show?id=c0c9e520310' target=_blank style='color:#2F92EE;'>#移植物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75203, encryptionId=c0c9e520310, topicName=移植物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=153620156575, createdName=10518100zz, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342922, encodeId=4507342922c9, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed Sep 05 19:06:57 CST 2018, time=2018-09-05, status=1, ipAttribution=)]
    2018-09-07 wincls
  6. 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  7. 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href='/topic/show?id=a798e520582' target=_blank style='color:#2F92EE;'>#移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75205, encryptionId=a798e520582, topicName=移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4d6c3527534, createdName=手留余香, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487465, encodeId=c0e1148e465f4, content=<a href='/topic/show?id=ba951352387' target=_blank style='color:#2F92EE;'>#OTC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13523, encryptionId=ba951352387, topicName=OTC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b36f8313624, createdName=ymljack, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578847, encodeId=821c15e8847f5, content=<a href='/topic/show?id=7e74536097a' target=_blank style='color:#2F92EE;'>#慢性移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53609, encryptionId=7e74536097a, topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620722, encodeId=55721620e22a4, content=<a href='/topic/show?id=c0c9e520310' target=_blank style='color:#2F92EE;'>#移植物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75203, encryptionId=c0c9e520310, topicName=移植物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=153620156575, createdName=10518100zz, createdTime=Fri Sep 07 07:46:00 CST 2018, time=2018-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342922, encodeId=4507342922c9, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed Sep 05 19:06:57 CST 2018, time=2018-09-05, status=1, ipAttribution=)]
    2018-09-07 ymljack
  8. 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  9. 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  10. 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    2018-09-05 1e145228m78(暂无匿称)

    学习了,谢谢作者分享!

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