Science Advances :重大进展!延边大学等多单位合作,发现结肠炎的新干预策略

2020-10-25 枫叶 iNature

溃疡性结肠炎和克罗恩氏病是人类炎性肠病(IBD)的最常见形式。尽管确切的病因仍然未知,但是IBD的发展被广泛认为是遗传和环境因素共同决定的结果。

溃疡性结肠炎和克罗恩氏病是人类炎性肠病(IBD)的最常见形式。尽管确切的病因仍然未知,但是IBD的发展被广泛认为是遗传和环境因素共同决定的结果。右旋糖酐硫酸钠(DSS)诱发的小鼠急性结肠炎在探索人IBD的发病机理和治疗方法方面已经非常有效。但是,尚不清楚DSS诱导响应的结肠组织内NLRP3炎性体过度活化的因素。

2020年10月21日,延边大学张庆镐,陆军军医大学吴玉章,陈永文及重庆市急救医疗中心/重庆大学附属中心医院黄健共同通讯(延边大学为第一单位)在Science Advances 在线发表题为“CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation”的研究论文,该研究发现CD1d1缺乏症或巨噬细胞中CD1d1特定缺失的小鼠(LymCD1d1-/-)对DSS诱导的急性结肠炎有抵抗力。这种保护作用归因于NLRP3的结肠生物合成以及炎性体底物IL-1β和IL-18的增加。进一步的研究表明,iGb3占用CD1d1会引发细胞内域Ser330去磷酸化,从而导致通过AKT-STAT1-过氧化物酶1(PRDX1)-核因子κB(NF-κB)减少信号级联,最终下调巨噬细胞中的Nlrp3,Il1b和Il18基因表达。

因此,CD1d1在巨噬细胞中的平衡作用似乎决定了DSS介导的结肠炎在小鼠中的严重性。这些发现提出了治疗IBD和其他炎性疾病的新干预策略。

溃疡性结肠炎和克罗恩氏病是人类炎性肠病(IBD)的最常见形式。尽管确切的病因仍然未知,但是IBD的发展被广泛认为是遗传和环境因素共同决定的结果。通过在动物中口服右旋糖酐硫酸钠(DSS)来建立实验性结肠炎模型,以诱导人IBD样临床综合征,表现为粘蛋白耗竭,上皮变性,凋亡和肠道菌群失调。DSS诱发的小鼠急性结肠炎在探索人IBD的发病机理和治疗方法方面已经非常有效。

小鼠CD1d1通过与主要组织相容性复合体(MHC)分子共享结构和功能同源性而属于CD1d超家族蛋白。CD1d1通过呈递抗原性自身脂质或某些源自病原性细菌,共生动物和真菌的糖脂,特异性激活一群称为自然杀伤性T(NKT)的非常规T细胞。CD1d1在DSS介导的结肠炎的发病机理中的功能研究已产生争议的结果,一项工作表明CD1d1-/-小鼠在DSS结肠炎的发展方面没有差异,而其他一些报道称CD1d1-/-小鼠是DSS结肠炎的发病机制。尽管这种差异的基础尚不清楚,但似乎CD1d1在不同细胞类型上的表达可能在控制急性结肠炎的进展中具有多种生物学功能。

NLRP3(含3个NLR家族的吡啶结构域)炎性小体是一种多蛋白复合物,包含NLRP3,caspase-1和衔接子分子ASC。一旦被激活,炎症小体通过分别催化前体proIL-1β和proIL-18分别转化为活性IL-1β和IL-18来触发休眠procaspase-1蛋白水解切割为活性caspase-1。NLRP3的失调通常与包括IBD在内的炎性疾病的恶化有关。例如,NLRP3基因中的单核苷酸多态性与溃疡性结肠炎的易感性有关。但是,尚不清楚DSS诱导响应的结肠组织内NLRP3炎性体过度活化的因素。

在这里显示具有CD1d1缺乏症或巨噬细胞中CD1d1特定缺失的小鼠(LymCD1d1-/-)对DSS诱导的急性结肠炎有抵抗力。这种保护作用归因于NLRP3的结肠生物合成以及炎性体底物IL-1β和IL-18的增加。进一步的研究表明,iGb3占用CD1d1会引发细胞内域Ser330去磷酸化,从而导致通过AKT-STAT1-过氧化物酶1(PRDX1)-核因子κB(NF-κB)减少信号级联,最终下调巨噬细胞中的Nlrp3,Il1b和Il18基因表达。

因此,CD1d1在巨噬细胞中的平衡作用似乎决定了DSS介导的结肠炎在小鼠中的严重性。这些发现提出了治疗IBD和其他炎性疾病的新干预策略。

原始出处:

Shan Cui, Chenhui Wang, Weizhi Bai, et al.CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation.Sci Adv. 2020 Oct 21;6(43):eaaz7290. doi: 10.1126/sciadv.aaz7290. Print 2020 Oct.

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    2020-10-27 docwu2019
  4. [GetPortalCommentsPageByObjectIdResponse(id=2041961, encodeId=f46c20419610e, content=<a href='/topic/show?id=faf84881902' target=_blank style='color:#2F92EE;'>#干预策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48819, encryptionId=faf84881902, topicName=干预策略)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sun Dec 13 11:37:39 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1814543, encodeId=be201814543c5, content=<a href='/topic/show?id=f72795e80d0' target=_blank style='color:#2F92EE;'>#重大进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95780, encryptionId=f72795e80d0, topicName=重大进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b96f328, createdName=wwzzly, createdTime=Wed Nov 04 05:37:39 CST 2020, time=2020-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376194, encodeId=151513e61947e, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 27 08:37:39 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894419, encodeId=83a8894419b9, content=加油,早起成功!, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201025/6855c11d03d14ffe9821c390a8212f6a/4a122e6cdf4f4857a3a1ced2063770bd.jpg, createdBy=0ce587510, createdName=narutohokage, createdTime=Sun Oct 25 22:30:22 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894378, encodeId=ebfd8943e85f, content=对炎性肠病有了认识, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200729/2ee0ca079ce64987b1195eb6aa20a1f4/ae923a98c9704879bacdc81d9fa7479a.jpg, createdBy=a3ab5398909, createdName=ms6000001113694287, createdTime=Sun Oct 25 19:44:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894367, encodeId=a1d589436e91, content=有用!, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f0d45220203, createdName=1477a9cbm52暂无昵称, createdTime=Sun Oct 25 18:26:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894366, encodeId=f79889436693, content=有收获, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:08:01 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894365, encodeId=b3358943651f, content=好文章 收获满满, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:07:47 CST 2020, time=2020-10-25, status=1, ipAttribution=)]
    2020-10-25 narutohokage

    加油,早起成功!

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2041961, encodeId=f46c20419610e, content=<a href='/topic/show?id=faf84881902' target=_blank style='color:#2F92EE;'>#干预策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48819, encryptionId=faf84881902, topicName=干预策略)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sun Dec 13 11:37:39 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1814543, encodeId=be201814543c5, content=<a href='/topic/show?id=f72795e80d0' target=_blank style='color:#2F92EE;'>#重大进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95780, encryptionId=f72795e80d0, topicName=重大进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b96f328, createdName=wwzzly, createdTime=Wed Nov 04 05:37:39 CST 2020, time=2020-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376194, encodeId=151513e61947e, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 27 08:37:39 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894419, encodeId=83a8894419b9, content=加油,早起成功!, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201025/6855c11d03d14ffe9821c390a8212f6a/4a122e6cdf4f4857a3a1ced2063770bd.jpg, createdBy=0ce587510, createdName=narutohokage, createdTime=Sun Oct 25 22:30:22 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894378, encodeId=ebfd8943e85f, content=对炎性肠病有了认识, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200729/2ee0ca079ce64987b1195eb6aa20a1f4/ae923a98c9704879bacdc81d9fa7479a.jpg, createdBy=a3ab5398909, createdName=ms6000001113694287, createdTime=Sun Oct 25 19:44:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894367, encodeId=a1d589436e91, content=有用!, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f0d45220203, createdName=1477a9cbm52暂无昵称, createdTime=Sun Oct 25 18:26:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894366, encodeId=f79889436693, content=有收获, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:08:01 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894365, encodeId=b3358943651f, content=好文章 收获满满, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:07:47 CST 2020, time=2020-10-25, status=1, ipAttribution=)]
    2020-10-25 ms6000001113694287

    对炎性肠病有了认识

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2041961, encodeId=f46c20419610e, content=<a href='/topic/show?id=faf84881902' target=_blank style='color:#2F92EE;'>#干预策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48819, encryptionId=faf84881902, topicName=干预策略)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sun Dec 13 11:37:39 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1814543, encodeId=be201814543c5, content=<a href='/topic/show?id=f72795e80d0' target=_blank style='color:#2F92EE;'>#重大进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95780, encryptionId=f72795e80d0, topicName=重大进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b96f328, createdName=wwzzly, createdTime=Wed Nov 04 05:37:39 CST 2020, time=2020-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376194, encodeId=151513e61947e, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 27 08:37:39 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894419, encodeId=83a8894419b9, content=加油,早起成功!, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201025/6855c11d03d14ffe9821c390a8212f6a/4a122e6cdf4f4857a3a1ced2063770bd.jpg, createdBy=0ce587510, createdName=narutohokage, createdTime=Sun Oct 25 22:30:22 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894378, encodeId=ebfd8943e85f, content=对炎性肠病有了认识, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200729/2ee0ca079ce64987b1195eb6aa20a1f4/ae923a98c9704879bacdc81d9fa7479a.jpg, createdBy=a3ab5398909, createdName=ms6000001113694287, createdTime=Sun Oct 25 19:44:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894367, encodeId=a1d589436e91, content=有用!, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f0d45220203, createdName=1477a9cbm52暂无昵称, createdTime=Sun Oct 25 18:26:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894366, encodeId=f79889436693, content=有收获, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:08:01 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894365, encodeId=b3358943651f, content=好文章 收获满满, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:07:47 CST 2020, time=2020-10-25, status=1, ipAttribution=)]
    2020-10-25 1477a9cbm52暂无昵称

    有用!

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2041961, encodeId=f46c20419610e, content=<a href='/topic/show?id=faf84881902' target=_blank style='color:#2F92EE;'>#干预策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48819, encryptionId=faf84881902, topicName=干预策略)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sun Dec 13 11:37:39 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1814543, encodeId=be201814543c5, content=<a href='/topic/show?id=f72795e80d0' target=_blank style='color:#2F92EE;'>#重大进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95780, encryptionId=f72795e80d0, topicName=重大进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b96f328, createdName=wwzzly, createdTime=Wed Nov 04 05:37:39 CST 2020, time=2020-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376194, encodeId=151513e61947e, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 27 08:37:39 CST 2020, time=2020-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894419, encodeId=83a8894419b9, content=加油,早起成功!, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201025/6855c11d03d14ffe9821c390a8212f6a/4a122e6cdf4f4857a3a1ced2063770bd.jpg, createdBy=0ce587510, createdName=narutohokage, createdTime=Sun Oct 25 22:30:22 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894378, encodeId=ebfd8943e85f, content=对炎性肠病有了认识, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200729/2ee0ca079ce64987b1195eb6aa20a1f4/ae923a98c9704879bacdc81d9fa7479a.jpg, createdBy=a3ab5398909, createdName=ms6000001113694287, createdTime=Sun Oct 25 19:44:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894367, encodeId=a1d589436e91, content=有用!, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f0d45220203, createdName=1477a9cbm52暂无昵称, createdTime=Sun Oct 25 18:26:21 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894366, encodeId=f79889436693, content=有收获, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:08:01 CST 2020, time=2020-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=894365, encodeId=b3358943651f, content=好文章 收获满满, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2205223096, createdName=1478419fm01(暂无昵称), createdTime=Sun Oct 25 18:07:47 CST 2020, time=2020-10-25, status=1, ipAttribution=)]
    2020-10-25 1478419fm01(暂无昵称)

    有收获

    0

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