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Diabetologia：胰岛素原肽可促进自身免疫性糖尿病？

2019-12-28 MedSci MedSci原创

自身免疫糖尿病
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最近对儿童的自然史研究表明，特定的HLA基因型与免疫反应的第一个抗原靶点之间存在联系。然而目前，关于特异性HLA分子对1型糖尿病等自身免疫性疾病病理影响的分子基础尚不清楚。本研究以一种常见的糖尿病相关HLA单倍型为背景，通过探讨胰岛抗原的致糖尿病性来研究这种体内联系。

最近对儿童的自然史研究表明，特定的HLA基因型与免疫反应的第一个抗原靶点之间存在联系。然而目前，关于特异性HLA分子对1型糖尿病等自身免疫性疾病病理影响的分子基础尚不清楚。本研究以一种常见的糖尿病相关HLA单倍型为背景，通过探讨胰岛抗原的致糖尿病性来研究这种体内联系。

研究人员建立了一种新型的hla转基因小鼠模型，该模型在C57BL/6背景下表达1型糖尿病高危基因(DRB1*03:01-DQA1*05:01-DQB1*02:01)以及大鼠胰岛素启动子和人类CD4下的人类CD80。用添加佐剂的抗原引物检测候选抗原和肽的致糖尿病性。

研究结果显示，b7.1 +小鼠自发发展为自身免疫性糖尿病(35周龄时发病率为46%)，伴有许多人类1型糖尿病的特征(针对GAD65和胰岛素原的自身抗体;胰岛被CD4+、CD8+ B220+、CD11b+和CD11c+免疫细胞浸润)。添加佐剂的前胰岛素抗原启动后，疾病明显加速，外显率更高(平均发病11周，攻后20周发生率100%)。此外，胰岛素原的致糖尿病作用位于B29-C11的15位残基区。

本研究使用体内模型鉴定了在HLA-DR3-DQ2背景上高度致糖尿病的胰岛素原衍生肽区域。 这种方法和经过此方法确定的肽区域可能对人类1型糖尿病的未来研究具有更广泛的意义。

原始出处：

Johan Verhagen，Norkhairin Yusuf，Proinsulin peptide promotes autoimmune diabetes in a novel HLA-DR3-DQ2-transgenic murine model of spontaneous disease

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    2020-08-09 baoya

    #胰岛#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1750125, encodeId=be891e50125d8, content=<a href='/topic/show?id=be7c8385345' target=_blank style='color:#2F92EE;'>#胰岛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83853, encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Sun Aug 09 03:31:00 CST 2020, time=2020-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639312, encodeId=00441639312a9, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, 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=Mon Nov 09 00:31:00 CST 2020, time=2020-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761279, encodeId=bbcf1e61279a0, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Fri Jun 19 04:31:00 CST 2020, time=2020-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1042900, encodeId=28bf104290052, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sat Dec 28 16:31:00 CST 2019, time=2019-12-28, status=1, ipAttribution=)]
    2020-11-09 ms9608593228839890

    #DIA#

    0

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    2020-06-19 ms5439512287675881

    #BET#

    0

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    2019-12-28 misszhang

    谢谢MedSci提供最新的资讯

    0

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