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Sci Rep:强直性脊柱炎中通过靶向Janus激酶抑制离体Th17应答

2018-10-27 xiangting MedSci原创

因为它们可以同时抑制多种Th17细胞因子,这些临床前数据表明JAK抑制剂是AS治疗试验中有前途的候选药。

强直性脊柱炎(AS)的治疗选择仍然有限。T辅助细胞17(Th17)通路已成为疾病发病的主要驱动因素和良好的治疗靶点。Janus激酶(JAK)是Th17细胞中细胞因子信号的关键转导因子,因此成为治疗AS有前途的靶标。这里研究了四种不同的JAK抑制剂对来自AS患者和健康对照者细胞的治疗潜力,这些细胞在Th17促进条件下在体外培养。

通过ELISA评估IL-17A、IL-17F、IL-22、GM-CSF和IFNγ水平,使用磷酸特异化流式细胞术研究抑制作用。siRNA使得CD4+ T细胞中的JAK1/2/3和TYK2沉默,并通过ELISA(IL-17A、IL-17F和IL-22)、Western印迹,qPCR和磷酸特异化流式细胞术分析效应。具有不同特异性的JAK抑制剂在体外抑制CD4+T淋巴细胞产生多种Th17细胞因子(IL-17A、IL-17F和IL-22),JAK1-3和Tyk2沉默也会抑制CD4+T淋巴细胞,并对细胞生存力或增殖没有影响。

因为它们可以同时抑制多种Th17细胞因子,这些临床前数据表明JAK抑制剂是AS治疗试验中有前途的候选药。改善TYK2或其他JAK亚型的靶向可以赋予AS中Th17应答的个体化效果。

原始出处:

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1946868, encodeId=7f9019468688d, content=<a href='/topic/show?id=9a3950183e9' target=_blank style='color:#2F92EE;'>#强直性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50183, encryptionId=9a3950183e9, topicName=强直性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKeia4TJeMGvEH3wKKIBNjuHuIic1HDNOB10j4tCd3nbylxkxm6HSMfEaKkSu6OZOak4uZv7UVicsWEg/132, createdBy=bc9a2500116, createdName=zywlvao, createdTime=Sat May 18 14:05:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354224, encodeId=db3c354224f3, content=这篇文章附有参考文献,1、表示对原作者尊敬。2、读者也可扩展学习,甚至中英对照,还可学习英语。而梅斯医学的其他类似文章都不附主要参考文献,实不可取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=526c2485304, createdName=12468bd3m60暂无昵称, createdTime=Sun Dec 02 07:43:03 CST 2018, time=2018-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351928, encodeId=08bf351928aa, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, 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=Thu Nov 08 09:11:26 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413563, encodeId=6b221413563a1, content=<a href='/topic/show?id=9cd21e364df' target=_blank style='color:#2F92EE;'>#Th17#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17364, encryptionId=9cd21e364df, topicName=Th17)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1440374, encodeId=47d114403e47b, content=<a href='/topic/show?id=6f0e845427f' target=_blank style='color:#2F92EE;'>#脊柱炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84542, encryptionId=6f0e845427f, topicName=脊柱炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=50834728424, createdName=1249898am16暂无昵称, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496037, encodeId=633a149603ecc, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=)]
    2019-05-18 zywlvao
  2. [GetPortalCommentsPageByObjectIdResponse(id=1946868, encodeId=7f9019468688d, content=<a href='/topic/show?id=9a3950183e9' target=_blank style='color:#2F92EE;'>#强直性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50183, encryptionId=9a3950183e9, topicName=强直性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKeia4TJeMGvEH3wKKIBNjuHuIic1HDNOB10j4tCd3nbylxkxm6HSMfEaKkSu6OZOak4uZv7UVicsWEg/132, createdBy=bc9a2500116, createdName=zywlvao, createdTime=Sat May 18 14:05:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354224, encodeId=db3c354224f3, content=这篇文章附有参考文献,1、表示对原作者尊敬。2、读者也可扩展学习,甚至中英对照,还可学习英语。而梅斯医学的其他类似文章都不附主要参考文献,实不可取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=526c2485304, createdName=12468bd3m60暂无昵称, createdTime=Sun Dec 02 07:43:03 CST 2018, time=2018-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351928, encodeId=08bf351928aa, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, 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=Thu Nov 08 09:11:26 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413563, encodeId=6b221413563a1, content=<a href='/topic/show?id=9cd21e364df' target=_blank style='color:#2F92EE;'>#Th17#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17364, encryptionId=9cd21e364df, topicName=Th17)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1440374, encodeId=47d114403e47b, content=<a href='/topic/show?id=6f0e845427f' target=_blank style='color:#2F92EE;'>#脊柱炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84542, encryptionId=6f0e845427f, topicName=脊柱炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=50834728424, createdName=1249898am16暂无昵称, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496037, encodeId=633a149603ecc, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=)]
    2018-12-02 12468bd3m60暂无昵称

    这篇文章附有参考文献,1、表示对原作者尊敬。2、读者也可扩展学习,甚至中英对照,还可学习英语。而梅斯医学的其他类似文章都不附主要参考文献,实不可取。

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1946868, encodeId=7f9019468688d, content=<a href='/topic/show?id=9a3950183e9' target=_blank style='color:#2F92EE;'>#强直性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50183, encryptionId=9a3950183e9, topicName=强直性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKeia4TJeMGvEH3wKKIBNjuHuIic1HDNOB10j4tCd3nbylxkxm6HSMfEaKkSu6OZOak4uZv7UVicsWEg/132, createdBy=bc9a2500116, createdName=zywlvao, createdTime=Sat May 18 14:05:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354224, encodeId=db3c354224f3, content=这篇文章附有参考文献,1、表示对原作者尊敬。2、读者也可扩展学习,甚至中英对照,还可学习英语。而梅斯医学的其他类似文章都不附主要参考文献,实不可取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=526c2485304, createdName=12468bd3m60暂无昵称, createdTime=Sun Dec 02 07:43:03 CST 2018, time=2018-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351928, encodeId=08bf351928aa, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, 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=Thu Nov 08 09:11:26 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413563, encodeId=6b221413563a1, content=<a href='/topic/show?id=9cd21e364df' target=_blank style='color:#2F92EE;'>#Th17#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17364, encryptionId=9cd21e364df, topicName=Th17)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1440374, encodeId=47d114403e47b, content=<a href='/topic/show?id=6f0e845427f' target=_blank style='color:#2F92EE;'>#脊柱炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84542, encryptionId=6f0e845427f, topicName=脊柱炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=50834728424, createdName=1249898am16暂无昵称, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496037, encodeId=633a149603ecc, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=)]
    2018-11-08 1e145228m78(暂无匿称)

    学习了,谢谢作者分享!

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1946868, encodeId=7f9019468688d, content=<a href='/topic/show?id=9a3950183e9' target=_blank style='color:#2F92EE;'>#强直性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50183, encryptionId=9a3950183e9, topicName=强直性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKeia4TJeMGvEH3wKKIBNjuHuIic1HDNOB10j4tCd3nbylxkxm6HSMfEaKkSu6OZOak4uZv7UVicsWEg/132, createdBy=bc9a2500116, createdName=zywlvao, createdTime=Sat May 18 14:05:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354224, encodeId=db3c354224f3, content=这篇文章附有参考文献,1、表示对原作者尊敬。2、读者也可扩展学习,甚至中英对照,还可学习英语。而梅斯医学的其他类似文章都不附主要参考文献,实不可取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=526c2485304, createdName=12468bd3m60暂无昵称, createdTime=Sun Dec 02 07:43:03 CST 2018, time=2018-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351928, encodeId=08bf351928aa, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, 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=Thu Nov 08 09:11:26 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413563, encodeId=6b221413563a1, content=<a href='/topic/show?id=9cd21e364df' target=_blank style='color:#2F92EE;'>#Th17#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17364, encryptionId=9cd21e364df, topicName=Th17)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1440374, encodeId=47d114403e47b, content=<a href='/topic/show?id=6f0e845427f' target=_blank style='color:#2F92EE;'>#脊柱炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84542, encryptionId=6f0e845427f, topicName=脊柱炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=50834728424, createdName=1249898am16暂无昵称, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496037, encodeId=633a149603ecc, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=)]
    2018-10-29 zhaojie88
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1946868, encodeId=7f9019468688d, content=<a href='/topic/show?id=9a3950183e9' target=_blank style='color:#2F92EE;'>#强直性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50183, encryptionId=9a3950183e9, topicName=强直性)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKeia4TJeMGvEH3wKKIBNjuHuIic1HDNOB10j4tCd3nbylxkxm6HSMfEaKkSu6OZOak4uZv7UVicsWEg/132, createdBy=bc9a2500116, createdName=zywlvao, createdTime=Sat May 18 14:05:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354224, encodeId=db3c354224f3, content=这篇文章附有参考文献,1、表示对原作者尊敬。2、读者也可扩展学习,甚至中英对照,还可学习英语。而梅斯医学的其他类似文章都不附主要参考文献,实不可取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=138, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=526c2485304, createdName=12468bd3m60暂无昵称, createdTime=Sun Dec 02 07:43:03 CST 2018, time=2018-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351928, encodeId=08bf351928aa, content=学习了,谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, 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=Thu Nov 08 09:11:26 CST 2018, time=2018-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413563, encodeId=6b221413563a1, content=<a href='/topic/show?id=9cd21e364df' target=_blank style='color:#2F92EE;'>#Th17#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17364, encryptionId=9cd21e364df, topicName=Th17)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1440374, encodeId=47d114403e47b, content=<a href='/topic/show?id=6f0e845427f' target=_blank style='color:#2F92EE;'>#脊柱炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84542, encryptionId=6f0e845427f, topicName=脊柱炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=50834728424, createdName=1249898am16暂无昵称, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496037, encodeId=633a149603ecc, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Oct 29 01:05:00 CST 2018, time=2018-10-29, status=1, ipAttribution=)]
    2018-10-29 redcrab

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