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Diabetologia：细胞外HMGB1通过损害调节性T细胞稳定性加剧自身免疫进展和1型糖尿病复发

2020-07-20 MedSci原创 MedSci原创

调节性T细胞；稳定性
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高迁移率组蛋白1 (HMGB1)是一种进化保守的染色体蛋白，一旦在细胞外释放，就会引起免疫系统响应。

高迁移率组蛋白1 (HMGB1)是一种进化保守的染色体蛋白，一旦在细胞外释放，就会引起免疫系统响应。因此，目前认为HMGB1有助于自身免疫性糖尿病的发病机制，但它对1型糖尿病的发病和进展的确切影响，以及相关的分子机制，还没有完全阐明。

在本研究中，我们以NOD小鼠为模型，研究阻断HMGB1对1型糖尿病的预防、治疗和逆转的影响。为了研究其作用机制，我们广泛研究了调控T细胞(Tregs)在HMGB1刺激下的特征及其相关信号通路。此外，我们调查了我们的数据与人类自身免疫性糖尿病的相关性。

研究结果显示，中和HMGB1不仅延迟了糖尿病发作，而且在20只新发糖尿病NOD小鼠中有13只逆转了糖尿病。在糖尿病NOD小鼠中，阻断HMGB1可以防止胰岛同种移植物自身免疫攻击。利用携带Foxp3家族报告基因结构的转基因报告基因小鼠，我们发现使用HMGB1会损害Treg的稳定性和功能。机制研究显示，HMGB1激活AGE受体(RAGE)和toll样受体(TLR)4，增强磷脂酰肌醇3-激酶(PI3K) - akt -雷帕霉素(mTOR)信号通路的机制靶点，从而削弱Treg的稳定性和功能。事实上，1型糖尿病患者体内高循环水平的HMGB1会导致Treg不稳定，这表明在临床环境中阻断HMGB1可能是对抗1型糖尿病的有效疗法。

研究结果表明，目前的数据支持HMGB1可能是一个可行的治疗靶点，以用于防止1型糖尿病患者自身免疫的启动、进展和复发。

原始出处：

Jing Zhang, Longmin Chen,Extracellular HMGB1 exacerbates autoimmune progression and recurrence of type 1 diabetes by impairing regulatory T cell stability

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    2021-03-05 jiangfeng5067

    #稳定性#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1900535, encodeId=a21819005359c, content=<a href='/topic/show?id=0983e529745' target=_blank style='color:#2F92EE;'>#稳定性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75297, encryptionId=0983e529745, topicName=稳定性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e0a1165, createdName=jiangfeng5067, createdTime=Fri Mar 05 22:16:33 CST 2021, time=2021-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639529, encodeId=a0d01639529ee, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sun Sep 27 20:16:33 CST 2020, time=2020-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761453, encodeId=e0ad1e6145390, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sat Oct 31 11:16:33 CST 2020, time=2020-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=803609, encodeId=8d228036097c, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>不太靠谱哦！, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Jul 21 00:35:16 CST 2020, time=2020-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043233, encodeId=58c010432332b, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Jul 20 17:16:33 CST 2020, time=2020-07-20, status=1, ipAttribution=)]
    2020-09-27 ms9608593228839890

    #DIA#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1900535, encodeId=a21819005359c, content=<a href='/topic/show?id=0983e529745' target=_blank style='color:#2F92EE;'>#稳定性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75297, encryptionId=0983e529745, topicName=稳定性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e0a1165, createdName=jiangfeng5067, createdTime=Fri Mar 05 22:16:33 CST 2021, time=2021-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639529, encodeId=a0d01639529ee, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sun Sep 27 20:16:33 CST 2020, time=2020-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761453, encodeId=e0ad1e6145390, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sat Oct 31 11:16:33 CST 2020, time=2020-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=803609, encodeId=8d228036097c, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>不太靠谱哦！, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Jul 21 00:35:16 CST 2020, time=2020-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043233, encodeId=58c010432332b, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Jul 20 17:16:33 CST 2020, time=2020-07-20, status=1, ipAttribution=)]
    2020-10-31 ms5439512287675881

    #BET#

    0

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    2020-07-21 lovetcm

    #糖尿病#不太靠谱哦！

    0

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    2020-07-20 misszhang

    谢谢MedSci提供最新的资讯

    0