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J Trauma Acute Care Surg:肠上皮细胞来源的外泌体触发创伤后免疫功能障碍

2017-12-03 MedSci MedSci原创

外泌体是作为免疫应答的内源性介质的细胞外囊泡。我们以前已经表明,在外伤/失血性休克(T/HS)后释放到肠系膜淋巴(ML)中的外泌体诱导巨噬细胞中促炎细胞因子的产生,并参与休克后急性肺损伤的发病机制。然而,ML外泌体的细胞来源及其在创伤后免疫应答中的作用仍不清楚。我们假设从受损肠上皮细胞(IECs)释放的外泌体通过改变树突细胞(DCs)(适应性免疫的关键调节剂)的功能来促进创伤后免疫功能障碍的发生。

外泌体是作为免疫应答的内源性介质的细胞外囊泡。我们以前已经表明,在外伤/失血性休克(T/HS)后释放到肠系膜淋巴(ML)中的外泌体诱导巨噬细胞中促炎细胞因子的产生,并参与休克后急性肺损伤的发病机制。然而,ML外泌体的细胞来源及其在创伤后免疫应答中的作用仍不清楚。我们假设从受损肠上皮细胞(IECs)释放的外泌体通过改变树突细胞(DCs)(适应性免疫的关键调节剂)的功能来促进创伤后免疫功能障碍的发生。

对雄性大鼠进行股动脉、颈静脉和ML导管的插管。开腹手术诱导T/HS,60分钟失血性休克,然后复苏。休克前和T/HS后收集ML以分离外泌体。通过流式细胞术评估从ML分离的外泌体的表面特征,以确定其细胞起源和表型变化。通过膜联蛋白V凋亡测定,共刺激分子的表达和对淋巴细胞的抗原呈递能力来评估ML外体对DC的免疫调节作用。

结果显示,从ML分离的外泌体高度表达CD63(外泌体标志物)和EpCAM(上皮细胞特异性标志物),表明它们来自IECs 。T/HS后ML外泌体免疫调节分子,如MHC II类分子和Fas配体,的表达显著增加。与T/HS后从ML分离的外泌体共培养后,DCs细胞的凋亡较休克前ML外泌体增加了2倍。此外,T/HS后 ML外泌体明显抑制LPS介导的DCs CD80和CD86的表达,并降低其诱导淋巴细胞增殖的抗原呈递能力。

综上所述,该研究结果表明,T/HS和复苏后,肠上皮细胞释放免疫调节性外泌体进入ML。 ML外泌体可能是创伤后免疫抑制导致DCs消耗和功能障碍的关键介质。

原始出处:

Kojima M, Costantini TW, et al., Gut Epithelial Cell-derived Exosomes Trigger Post-trauma Immune Dysfunction. J Trauma Acute Care Surg. 2017 Nov 21. doi: 10.1097/TA.0000000000001748. 

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    2018-04-04 bsmagic9140
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    2018-06-18 siiner
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  5. 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    2017-12-05 bshuang
  6. 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16:50:43 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=266474, encodeId=5aa32664e41d, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sun Dec 03 14:02:40 CST 2017, time=2017-12-03, status=1, ipAttribution=)]
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  9. 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    2017-12-03 三生有幸9135

    学习一下谢谢分享

    0

  10. 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    2017-12-03 131****1460

    学习了受益匪浅

    0

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目前普遍认为动脉粥样硬化是血管壁的慢性脂质引起的炎症。氧化低密度脂蛋白(oxLDL)驱动涉及巨噬细胞和内皮细胞(ECs)的动脉粥样化形成的发生。本研究既往研究发现表明,患者和动物模型收集的动脉粥样硬化斑块中,长非编码RNA生长停滞特异性5(lncRNA GAS5)的表达明显增加。本研究中,研究发现敲除lncRNA GAS5可降低oxLDL处理的THP-1细胞的凋亡。相反,oxLDL刺激后,lncR

只需 25 分钟!华人学者带来外泌体提取新突破

一种新型设备,能利用声波技术,快速从血液样品中分离外泌体(exosome)。在精准医疗时代,这项技术可能在未来的疾病诊断和治疗中发挥重要作用。外泌体里含有许多对疾病诊断具有重要作用的分子外泌体是细胞分泌的一种纳米级别的小囊泡,直径约为 30 至 150 纳米,它们携带重要的信息,包括蛋白质、miRNA 等,帮助细胞之间通信。以前的研究表明,外泌体内容物可以作为诸如癌症,神经变性疾病和肾脏疾病等疾病

Cell:科学家从外泌体中发现糖尿病胰岛素抵抗的机制

由肥胖导致的慢性组织炎症是胰岛素抵抗和2型糖尿病的根本原因。但迄今为止,其作用机制仍待阐明。在9月21日刊登在《细胞》杂志上的论文中,美国加州大学圣地亚哥分校(UCSD)医学院的研究人员确定了外泌体(Exosome),也即多种细胞分泌到胞外的极小的膜状脂质囊泡,是炎症和糖尿病之间缺失的环节。

Mol Cancer:实体瘤是如何克服厌氧环境促进癌细胞增殖和转移的?

为了克服实体肿瘤内部的缺氧微环境,肿瘤细胞会分泌含有大量的非编码RNA的外泌体促进肿瘤的进展和转移。然而,缺氧环境下肿瘤细胞分泌外泌体的确切机制尚未明了。本研究旨在探究缺氧环境是否可通过促进膀胱癌细胞分泌富含长链非编码RNA尿路上皮癌抗原1 (lncRNA-UCA1)的外泌体影响肿瘤的生长和进展。研究人员选择lncRNA-UCA1高表达的膀胱癌5637细胞作为外泌体生成的细胞,以及lncRNA-U

Cell:外泌体是代谢疾病中被忽视的关键因素

9月21日在线发表在Cell上的一篇论文报道了:加州大学圣地亚哥分校医学院的研究人员发现外泌体是连接肥胖引起的慢性组织炎症与胰岛素抵抗和2型糖尿病的重要环节。他们确定了脂肪组织外泌体中的一个关键miRNA,并将继续对其余的进行测序。

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