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Immunity：IL-22调节回肠炎感染应中IL-18的产生

2015-03-03 佚名 生物谷

肠炎感染
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肠道球虫感染会引起回肠炎，在此过程中宿主会产生Th1型免疫反应，典型的细胞因子包括IL-12，IFN-γ，TNF-α等。IL-18是一类参与Th1免疫反应的调节型细胞因子。之前的研究认为IL-18mRNA以及proIL-18在骨髓细胞以及上皮细胞中稳定性表达，然而其进一步切割与激活需要依赖炎症小体以及caspase的活性。另外，有报道认为IL-22参与了肠道球虫引起的回肠炎免疫反应。IL-

肠道球虫感染会引起回肠炎，在此过程中宿主会产生Th1型免疫反应，典型的细胞因子包括IL-12，IFN-γ，TNF-α等。IL-18是一类参与Th1免疫反应的调节型细胞因子。之前的研究认为IL-18mRNA以及proIL-18在骨髓细胞以及上皮细胞中稳定性表达，然而其进一步切割与激活需要依赖炎症小体以及caspase的活性。另外，有报道认为IL-22参与了肠道球虫引起的回肠炎免疫反应。IL-22由IL-23刺激产生，广泛表达于肠道T helper细胞以及先天淋巴细胞（ILC）中，而IL-22受体主要表达于表皮细胞。
 
对于IL-22是如何调节肠道球虫感染过程中宿主的免疫反应，美国genetech公司的Wenjun Ouyang课题组最近在immunity杂志发表了他们的研究成果。
 
首先，她们通过比较野生型小鼠与IL-22-/-小鼠在抗肠道球虫免疫反应的相关特征，发现突变体小鼠回肠组织中IL-18 mRNA的表达量较野生型有明显下降，蛋白水平的检测与组织学检测也得到了相同的结果。这一结果说明IL-22调控了小鼠在肠道球虫免疫反应过程中IL-18的产生。
 
随后，作者通过体内感染实验发现，突变体小鼠Th1细胞的活化程度，IFN-γ的分泌量以及中性粒细胞的浸入量较野生型都有明显下降。这一结果说明IL-22-/-小鼠在肠道球虫感染过程中Th1免疫反应能力受到了抑制。
 
之后，作者发现体外利用IL-22刺激野生小鼠的回肠壁上皮细胞培养物能够激发IL-18 mRNA的产生与pro-IL-18的表达。然而IL-22受体缺失突变小鼠则不会受到IL-22的影响。以上结果说明IL-22能够直接激发IL-18的产生。另外，IL-22的激活名不能促进IL-18的切割与成熟。这一过程受到caspase-1以及ASC但并不受到NLRP3炎症小体的调控。
 
作者通过相似的实验发现，在没有肠道球虫的刺激时，IL-22或IL-22受体的缺失会导致IL-18稳态分泌的破坏。而这一特征只在回肠中出现。作者通过利用经典的PAMP对不同小鼠回肠表皮细胞进行刺激，结果显示，像Flaglin，LPS等物质均能够在野生型小鼠中引起pro-IL-18的表达，而在IL-22-/-小鼠中则没有这一特征。另外，作者通过遗传学手段证明IL-22引起的pro-IL-18的表达并不依赖于TLR经典通路中的关键蛋白MyD88，同时利用无菌小鼠实验证明这一过程也不依赖于肠道微生物。
 
之后，作者发现在肠道球虫感染环境下，IL-18也能够反向促进ILC分泌IL-22。另外，在柠檬酸杆菌感染中，IL-22也调控了IL-18的产生。
 
综上，这篇研究揭示了IL-22调控IL-18表达的这一事实，为宿主抗感染治疗提供了新的线索。

原始出处

Muñoz M1, Eidenschenk C2, Ota N2, Wong K2, Lohmann U1, Kühl AA3, Wang X2, Manzanillo P2, Li Y2, Rutz S2, Zheng Y2, Diehl L4, Kayagaki N5, van Lookeren-Campagne M2, Liesenfeld O1, Heimesaat M1, Ouyang W6.Interleukin-22 Induces Interleukin-18 Expression from Epithelial Cells during Intestinal Infection.Immunity. 2015 Feb 17;

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    2016-01-05 12498d2fm51(暂无昵称)

    #Immunity#

    0

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    2015-03-31 x35042875

    这篇研究揭示了IL-22调控IL-18表达的这一事实，为宿主抗感染治疗提供了新的线索。

    0

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    2015-03-05 jjjiang0202

    #IL-1#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2030292, encodeId=92262030292ff, content=<a href='/topic/show?id=25079e7287' target=_blank style='color:#2F92EE;'>#Immunity#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9772, encryptionId=25079e7287, topicName=Immunity)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Tue Jan 05 03:11:00 CST 2016, time=2016-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=19184, encodeId=e5e8191845d, content=这篇研究揭示了IL-22调控IL-18表达的这一事实，为宿主抗感染治疗提供了新的线索。, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508169, encodeId=2a8c150816916, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511331, encodeId=b687151133116, content=<a href='/topic/show?id=d47d40542cc' target=_blank style='color:#2F92EE;'>#回肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40542, encryptionId=d47d40542cc, topicName=回肠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9b1110335485, createdName=Tamikia, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553788, encodeId=d7721553e8813, content=<a href='/topic/show?id=f3e6964ea7' target=_blank style='color:#2F92EE;'>#IL-18#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9647, encryptionId=f3e6964ea7, topicName=IL-18)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bd614435976, createdName=wangbingxhy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585516, encodeId=848d158551681, content=<a href='/topic/show?id=b96996549f' target=_blank style='color:#2F92EE;'>#IL-22#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9654, encryptionId=b96996549f, topicName=IL-22)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=663217217672, createdName=smartjoy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626023, encodeId=c1c716260235f, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=)]
    2015-03-05 Tamikia

    #回肠#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2030292, encodeId=92262030292ff, content=<a href='/topic/show?id=25079e7287' target=_blank style='color:#2F92EE;'>#Immunity#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9772, encryptionId=25079e7287, topicName=Immunity)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Tue Jan 05 03:11:00 CST 2016, time=2016-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=19184, encodeId=e5e8191845d, content=这篇研究揭示了IL-22调控IL-18表达的这一事实，为宿主抗感染治疗提供了新的线索。, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508169, encodeId=2a8c150816916, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511331, encodeId=b687151133116, content=<a href='/topic/show?id=d47d40542cc' target=_blank style='color:#2F92EE;'>#回肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40542, encryptionId=d47d40542cc, topicName=回肠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9b1110335485, createdName=Tamikia, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553788, encodeId=d7721553e8813, content=<a href='/topic/show?id=f3e6964ea7' target=_blank style='color:#2F92EE;'>#IL-18#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9647, encryptionId=f3e6964ea7, topicName=IL-18)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bd614435976, createdName=wangbingxhy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585516, encodeId=848d158551681, content=<a href='/topic/show?id=b96996549f' target=_blank style='color:#2F92EE;'>#IL-22#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9654, encryptionId=b96996549f, topicName=IL-22)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=663217217672, createdName=smartjoy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626023, encodeId=c1c716260235f, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=)]
    2015-03-05 wangbingxhy

    #IL-18#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2030292, encodeId=92262030292ff, content=<a href='/topic/show?id=25079e7287' target=_blank style='color:#2F92EE;'>#Immunity#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9772, encryptionId=25079e7287, topicName=Immunity)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Tue Jan 05 03:11:00 CST 2016, time=2016-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=19184, encodeId=e5e8191845d, content=这篇研究揭示了IL-22调控IL-18表达的这一事实，为宿主抗感染治疗提供了新的线索。, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508169, encodeId=2a8c150816916, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511331, encodeId=b687151133116, content=<a href='/topic/show?id=d47d40542cc' target=_blank style='color:#2F92EE;'>#回肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40542, encryptionId=d47d40542cc, topicName=回肠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9b1110335485, createdName=Tamikia, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553788, encodeId=d7721553e8813, content=<a href='/topic/show?id=f3e6964ea7' target=_blank style='color:#2F92EE;'>#IL-18#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9647, encryptionId=f3e6964ea7, topicName=IL-18)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bd614435976, createdName=wangbingxhy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585516, encodeId=848d158551681, content=<a href='/topic/show?id=b96996549f' target=_blank style='color:#2F92EE;'>#IL-22#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9654, encryptionId=b96996549f, topicName=IL-22)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=663217217672, createdName=smartjoy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626023, encodeId=c1c716260235f, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=)]
    2015-03-05 smartjoy

    #IL-22#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2030292, encodeId=92262030292ff, content=<a href='/topic/show?id=25079e7287' target=_blank style='color:#2F92EE;'>#Immunity#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9772, encryptionId=25079e7287, topicName=Immunity)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Tue Jan 05 03:11:00 CST 2016, time=2016-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=19184, encodeId=e5e8191845d, content=这篇研究揭示了IL-22调控IL-18表达的这一事实，为宿主抗感染治疗提供了新的线索。, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508169, encodeId=2a8c150816916, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511331, encodeId=b687151133116, content=<a href='/topic/show?id=d47d40542cc' target=_blank style='color:#2F92EE;'>#回肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40542, encryptionId=d47d40542cc, topicName=回肠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9b1110335485, createdName=Tamikia, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1553788, encodeId=d7721553e8813, content=<a href='/topic/show?id=f3e6964ea7' target=_blank style='color:#2F92EE;'>#IL-18#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9647, encryptionId=f3e6964ea7, topicName=IL-18)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bd614435976, createdName=wangbingxhy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585516, encodeId=848d158551681, content=<a href='/topic/show?id=b96996549f' target=_blank style='color:#2F92EE;'>#IL-22#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9654, encryptionId=b96996549f, topicName=IL-22)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=663217217672, createdName=smartjoy, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626023, encodeId=c1c716260235f, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Mar 05 00:11:00 CST 2015, time=2015-03-05, status=1, ipAttribution=)]
    2015-03-05 tomyang93

    #IL-2#

    0