Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells.
Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells.
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DOI：
10.1016/j.redox.2018.06.009
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发表时间：
2018-09
期刊：
影响因子：
11.4
通讯作者：
Deshane JS
中科院分区：
文献类型：
--
作者：
Hough KP;Trevor JL;Strenkowski JG;Wang Y;Chacko BK;Tousif S;Chanda D;Steele C;Antony VB;Dokland T;Ouyang X;Zhang J;Duncan SR;Thannickal VJ;Darley-Usmar VM;Deshane JS
涉及先天性和适应性免疫细胞的慢性炎症与哮喘的发病机制有关。细胞间通讯对于驱动和解决哮喘炎症反应至关重要。新兴的研究表明，细胞外囊泡（EV），包括外来体促进这一过程。在这份报告中，我们使用了一系列的方法来证明EV含有来自供体细胞的线粒体标记物，这些标记物能够维持膜电位。此外，我们建议这些参与细胞间的沟通与哮喘的人类受试者的气道内。健康志愿者和哮喘患者的支气管肺泡灌洗液中均含有线粒体包裹的EV;然而，哮喘患者中含有线粒体的HLA-DR+ EV %和EV内线粒体DNA水平显著较高。此外，线粒体存在于来源于气道髓源性调节细胞（MDRC）的促炎性HLA-DR+亚群的外来体中，其是哮喘中T细胞应答的已知调节剂。使用共培养系统，在受体外周T细胞中发现了用MitoTracker绿色标记的外泌体，或来源于用CellLight线粒体GFP转导的MDRC的外泌体，支持直接外泌体介导的细胞-细胞转移。重要的是，外泌体转移的线粒体与线粒体网络共定位，并在受体T细胞内产生活性氧。这些发现支持了一种潜在的细胞间通讯的新机制，涉及线粒体的外泌体转移和靶细胞的生物能和/或氧化还原调节。BAL和MDRC来源的外泌体含有线粒体。呼吸道外泌体含有mtDNA。MDRC衍生的外泌体将线粒体转移至CD 4 + T细胞。外泌体线粒体与宿主细胞线粒体共定位。
Chronic inflammation involving both innate and adaptive immune cells is implicated in the pathogenesis of asthma. Intercellular communication is essential for driving and resolving inflammatory responses in asthma. Emerging studies suggest that extracellular vesicles (EVs) including exosomes facilitate this process. In this report, we have used a range of approaches to show that EVs contain markers of mitochondria derived from donor cells which are capable of sustaining a membrane potential. Further, we propose that these participate in intercellular communication within the airways of human subjects with asthma. Bronchoalveolar lavage fluid of both healthy volunteers and asthmatics contain EVs with encapsulated mitochondria; however, the % HLA-DR+ EVs containing mitochondria and the levels of mitochondrial DNA within EVs were significantly higher in asthmatics. Furthermore, mitochondria are present in exosomes derived from the pro-inflammatory HLA-DR+ subsets of airway myeloid-derived regulatory cells (MDRCs), which are known regulators of T cell responses in asthma. Exosomes tagged with MitoTracker Green, or derived from MDRCs transduced with CellLight Mitochondrial GFP were found in recipient peripheral T cells using a co-culture system, supporting direct exosome-mediated cell-cell transfer. Importantly, exosomally transferred mitochondria co-localize with the mitochondrial network and generate reactive oxygen species within recipient T cells. These findings support a potential novel mechanism of cell-cell communication involving exosomal transfer of mitochondria and the bioenergetic and/or redox regulation of target cells. BAL and MDRC-derived exosomes contain mitochondria. Airway exosomes contain mtDNA. MDRC-derived exosomes transfer mitochondria to CD4+ T cells. Exosomal mitochondria co-localize with host cell mitochondria.
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影响因子：
64.5
作者：
Boelens MC;Wu TJ;Nabet BY;Xu B;Qiu Y;Yoon T;Azzam DJ;Twyman-Saint Victor C;Wiemann BZ;Ishwaran H;Ter Brugge PJ;Jonkers J;Slingerland J;Minn AJ
通讯作者：
Minn AJ
影响因子：
3.7
作者：
Ben-Shachar, Dorit;Karry, Rachel
通讯作者：
Karry, Rachel
影响因子：
8
作者：
Deshane, J.;Zmijewski, J. W.;Chaplin, D. D.
通讯作者：
Chaplin, D. D.
DOI：
10.1152/ajplung.00155.2013
发表时间：
2014-05-01
影响因子：
4.9
作者：
Aravamudan, Bharathi;Kiel, Alexander;Prakash, Y. S.
通讯作者：
Prakash, Y. S.
DOI：
10.1152/ajplung.00165.2013
发表时间：
2013-11-01
影响因子：
4.9
作者：
Agarwal, Amit R.;Yin, Fei;Cadenas, Enrique
通讯作者：
Cadenas, Enrique