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A&R:CD163+ M2巨噬细胞通过Toll样受体7/IL-1受体相关激酶4/NF-κB信号通路促进IgG4相关疾病的纤维化

2022-05-12 MedSci原创 MedSci原创

CD163+ M2巨噬细胞通过TLR-7/IRAK4/NF-κB信号传导增加纤维化细胞因子的产生来促进IgG4相关疾病(IgG4-RD)中的纤维化。

    目的:IgG4相关疾病(IgG4-RD)是一种可影响多个器官的纤维炎症性疾病。该研究团队之前证明TLR7转基因C57BL/6小鼠的血清IgG1水平升高,唾液腺(SG)、肺和胰腺出现纤维化炎症。此外,研究人员在IgG4-RD患者的SG中观察到广泛的Toll样受体7(TLR-7)阳性CD163+ M2巨噬细胞浸润。进行这项研究以通过TLR-7途径检查纤维化机制。

    方法:使用DNA微阵列分析来自人类TLR7转基因小鼠和IgG4-RD患者的SG中的基因表达。研究人员从TLR7转基因小鼠和IgG4-RD患者的SG中提取了常见的上调TLR-7相关基因。最后研究了TLR-7激动剂洛索立滨刺激前后CD163+ M2巨噬细胞和成纤维细胞之间的相互作用。

    结果:在TLR7转基因小鼠和IgG4-RD患者中,IRAK3IRAK4显著过表达。与其他组相比,实时聚合酶链反应验证了仅IRAK4IgG4-RD患者中的上调(P<0.05)。在IgG4相关性泪腺炎和唾液腺炎患者的SG生发中心及其周围明显检测到白细胞介素1受体相关激酶4 (IRAK4)。双免疫荧光染色显示,IRAK4阳性细胞主要与SGs中的CD163+ M2巨噬细胞共定位(P<0.05)。用洛索立滨刺激后,CD163+ M2巨噬细胞表现出IRAK4NF-κB的表达显著增强,并且纤维化细胞因子的上清液浓度增加。最后,研究人员证实,在洛索立滨刺激后,用CD163+ M2巨噬细胞的上清液培养可增加成纤维细胞的数量(P<0.05

    结论:CD163+ M2巨噬细胞通过TLR-7/IRAK4/NF-κB信号传导增加纤维化细胞因子的产生来促进IgG4-RD中的纤维化。

 

出处:Chinju, A., Moriyama, M., Kakizoe-Ishiguro, et al. (2022), CD163+ M2 Macrophages Promote Fibrosis in IgG4-Related Disease Via Toll-like Receptor 7/Interleukin-1 Receptor–Associated Kinase 4/NF-κB Signaling. Arthritis Rheumatol, 74: 892-901. https://doi.org/10.1002/art.42043

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    2022-10-12 yeye5224612
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GetPortalCommentsPageByObjectIdResponse(id=1602781, encodeId=d9da1602e81c1, content=<a href='/topic/show?id=c41c11192e2' target=_blank style='color:#2F92EE;'>#M2巨噬细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11192, encryptionId=c41c11192e2, topicName=M2巨噬细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Thu May 12 02:19:15 CST 2022, time=2022-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615241, encodeId=bf1216152412a, content=<a href='/topic/show?id=010c9506a3' target=_blank style='color:#2F92EE;'>#IgG#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9506, encryptionId=010c9506a3, topicName=IgG)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c4f19588882, createdName=ms5768352621950538, createdTime=Thu May 12 02:19:15 CST 2022, time=2022-05-12, status=1, ipAttribution=)]
    2022-05-12 redcrab
  5. [GetPortalCommentsPageByObjectIdResponse(id=1946234, encodeId=7b8219462341d, content=<a href='/topic/show?id=001e12e38b2' target=_blank style='color:#2F92EE;'>#NF-κB信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12738, encryptionId=001e12e38b2, topicName=NF-κB信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=89da2500024, createdName=1194695146_61857347, createdTime=Sat Nov 26 12:19:15 CST 2022, time=2022-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1782714, encodeId=0d351e82714e9, content=<a href='/topic/show?id=fd1042e4ea' target=_blank style='color:#2F92EE;'>#CD16#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4274, encryptionId=fd1042e4ea, topicName=CD16)], attachment=null, authenticateStatus=null, createdAvatar=, 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createdName=ms5768352621950538, createdTime=Thu May 12 02:19:15 CST 2022, time=2022-05-12, status=1, ipAttribution=)]
    2022-05-12 jjjiang0202
  6. [GetPortalCommentsPageByObjectIdResponse(id=1946234, encodeId=7b8219462341d, content=<a href='/topic/show?id=001e12e38b2' target=_blank style='color:#2F92EE;'>#NF-κB信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12738, encryptionId=001e12e38b2, topicName=NF-κB信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=89da2500024, createdName=1194695146_61857347, createdTime=Sat Nov 26 12:19:15 CST 2022, time=2022-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1782714, encodeId=0d351e82714e9, content=<a href='/topic/show?id=fd1042e4ea' target=_blank style='color:#2F92EE;'>#CD16#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4274, encryptionId=fd1042e4ea, topicName=CD16)], attachment=null, authenticateStatus=null, createdAvatar=, 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createdName=ms5768352621950538, createdTime=Thu May 12 02:19:15 CST 2022, time=2022-05-12, status=1, ipAttribution=)]
  7. 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createdName=ms5768352621950538, createdTime=Thu May 12 02:19:15 CST 2022, time=2022-05-12, status=1, ipAttribution=)]
  8. 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