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J CLIN INVEST：T-bet+ B细胞导致系统性红斑狼疮等自体免疫疾病

2017-03-13 MedSci MedSci原创

自体免疫疾病B细胞T-bet+
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自身免疫性疾病是一种重要的疾病，如在美国其排在第三常见疾病之列。虽然可以通过药物缓解症状，但自身免疫性疾病并不能完全治愈，其发病机理也不甚明了。B细胞在自身免疫疾病，包括系统性红斑狼疮（SLE）中具有重要作用。然而，针对系统性红斑狼疮和类风湿性关节炎的临床试验中，靶向剔除患者B细胞的疗法只能改善部分病人的症状，并且得到改善的病人其病征并不统一。这一原因可能是，不分青红皂白地剔除B细胞而非致病性B细

自身免疫性疾病是一种重要的疾病，如在美国其排在第三常见疾病之列。虽然可以通过药物缓解症状，但自身免疫性疾病并不能完全治愈，其发病机理也不甚明了。B细胞在自身免疫疾病，包括系统性红斑狼疮（SLE）中具有重要作用。然而，针对系统性红斑狼疮和类风湿性关节炎的临床试验中，靶向剔除患者B细胞的疗法只能改善部分病人的症状，并且得到改善的病人其病征并不统一。这一原因可能是，不分青红皂白地剔除B细胞而非致病性B细胞，过于简单粗暴，总体上抑制了免疫系统。因为，作为重要的免疫系统的重要成员，B细胞同样对于免疫系统的稳定起着重要作用。于是，找到自身免疫疾病中致病性的B可能会给这一疗法提供新的思路。

Kira Rubtsova和同事的新研究表明，T-bet + B细胞促进自身抗体快速分泌，加重肾损伤，提高了SLE和狼疮肾炎模型小鼠的死亡率。 “这些数据表明，T-bet + B细胞就是致病B细胞亚群，它们可以作为SLE患者的新型治疗靶点。”这一发现最初源于研究人员发现CD11c + T-bet + B细胞普遍存在于在老年雌性小鼠以及自身免疫性疾病的患者以及对应的模型小鼠中。为了进一步探索这个亚群的B细胞对SLE和狼疮肾炎的具体作用，他们在SLE的三个小鼠模型（SLE1,2,3，会产生狼疮肾炎）中的B细胞中特异性地删除了。在这些去除了B细胞中T-bet的小鼠，没有形成自发生发中心，肾损伤程度减小（由无蛋白尿排出和肾小球损伤减少和IgG-C3复合物沉积的减少所证明），约1年的总自身抗体滴度减小，实验小鼠生存率也得到了提高。 B细胞中T-bet的缺失也降低了SLE小鼠中活化B细胞和T细胞的量。

Rubtsova和同事现在计划开发一种特异性靶向剔除T-bet + B细胞的药物。因为“这种药物对自身免疫性疾病患者具有巨大的优势，因为它只会特异性的剔除致病性B细胞，而不会如现有的疗法一样，也剔除其他无关的B细胞导致总体的免疫抑制“，Rubtsova说。

PS.那么这些细胞是怎么产生的呢？T-bet可是Th1，T细胞的标配呀，T-bet B细胞它不纠结吗？

原始出处：
Rubtsova, K. et al. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J. Clin. Invest.2017 Feb 27。

Andrea Aguilar.T-bet+ B cells mediate renal injury in lupus.Nature Reviews Nephrology.13 March 2017.doi:10.1038/nrneph.2017.38.

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    2017-11-03 xiangyuzhou971

    #EST#

    0

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    2017-10-16 qingrejiedu

    #系统性#

    0

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    2017-09-26 yuanming7

    #T-bet#

    0

  4. 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encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Thu Jun 29 12:55:00 CST 2017, time=2017-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=186483, encodeId=b69b186483af, content=细胞学说，新发现。, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kym1A9qicflExZYSdibSZBHDyicKZZj37w4jR44fPa9DI3mVLObHAxzntpTAbwxeHvviclcw8coNrDge/0, createdBy=6dc22001775, createdName=春暖花开8785, createdTime=Mon Apr 10 22:32:24 CST 2017, time=2017-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273186, encodeId=9e0612e3186d9, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387187, encodeId=bdae138e1878c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436092, encodeId=d576143609229, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511229, encodeId=a1df151122970, content=<a href='/topic/show?id=3f922910088' target=_blank style='color:#2F92EE;'>#免疫疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29100, encryptionId=3f922910088, topicName=免疫疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8a3610309283, createdName=晓辰, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-06-29 ms5439512287675881

    #BET#

    0

  5. 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channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387187, encodeId=bdae138e1878c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436092, encodeId=d576143609229, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511229, encodeId=a1df151122970, content=<a href='/topic/show?id=3f922910088' target=_blank style='color:#2F92EE;'>#免疫疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29100, encryptionId=3f922910088, topicName=免疫疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8a3610309283, createdName=晓辰, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-04-10 春暖花开8785

    细胞学说，新发现。

    0

  6. 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encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Thu Jun 29 12:55:00 CST 2017, time=2017-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=186483, encodeId=b69b186483af, content=细胞学说，新发现。, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kym1A9qicflExZYSdibSZBHDyicKZZj37w4jR44fPa9DI3mVLObHAxzntpTAbwxeHvviclcw8coNrDge/0, createdBy=6dc22001775, createdName=春暖花开8785, createdTime=Mon Apr 10 22:32:24 CST 2017, time=2017-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273186, encodeId=9e0612e3186d9, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387187, encodeId=bdae138e1878c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436092, encodeId=d576143609229, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511229, encodeId=a1df151122970, content=<a href='/topic/show?id=3f922910088' target=_blank style='color:#2F92EE;'>#免疫疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29100, encryptionId=3f922910088, topicName=免疫疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8a3610309283, createdName=晓辰, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-03-15 xiaoyeshuang

    #B细胞#

    0

  7. 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encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Thu Jun 29 12:55:00 CST 2017, time=2017-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=186483, encodeId=b69b186483af, content=细胞学说，新发现。, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kym1A9qicflExZYSdibSZBHDyicKZZj37w4jR44fPa9DI3mVLObHAxzntpTAbwxeHvviclcw8coNrDge/0, createdBy=6dc22001775, createdName=春暖花开8785, createdTime=Mon Apr 10 22:32:24 CST 2017, time=2017-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273186, encodeId=9e0612e3186d9, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387187, encodeId=bdae138e1878c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436092, encodeId=d576143609229, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511229, encodeId=a1df151122970, content=<a href='/topic/show?id=3f922910088' target=_blank style='color:#2F92EE;'>#免疫疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29100, encryptionId=3f922910088, topicName=免疫疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8a3610309283, createdName=晓辰, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-03-15 sunrural_42825357

    #狼疮#

    0

  8. 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href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511229, encodeId=a1df151122970, content=<a href='/topic/show?id=3f922910088' target=_blank style='color:#2F92EE;'>#免疫疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29100, encryptionId=3f922910088, topicName=免疫疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8a3610309283, createdName=晓辰, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-03-15 zhouqu_8

    #红斑#

    0

  9. 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createdAvatar=null, createdBy=8a3610309283, createdName=晓辰, createdTime=Wed Mar 15 14:55:00 CST 2017, time=2017-03-15, status=1, ipAttribution=)]
    2017-03-15 晓辰

    #免疫疾病#

    0

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