Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.
Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.
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DOI：
10.1371/journal.pone.0122991
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Askenase PW
中科院分区：
文献类型：
--
作者：
Bryniarski K;Ptak W;Martin E;Nazimek K;Szczepanik M;Sanak M;Askenase PW
经表皮和静脉注射半抗原双重免疫的小鼠淋巴结和脾脏细胞产生抑制成分，抑制介导接触敏感反应的效应T细胞的作用。我们最近在免疫系统中重新研究了这一现象。CD8+ T淋巴细胞衍生的外泌体通过B1a淋巴细胞产生的抗体轻链外泌体表面涂层将抑制性miR-150特异性地转移到效应T细胞。胞外RNA （exRNA）通过外泌体的载体或伴侣体来保护其免受血浆RNA酶的侵害。外泌体将功能性RNA转移到靶细胞的研究已经得到了很好的描述，而不含外泌体的外泌体的转移机制尚不清楚。在目前的研究中，我们描述了从外泌体中提取的细胞外miR-150，但仍然能够介导抗原特异性抑制。我们已经确定，这是由于miR-150与效应T细胞的B1a细胞伴侣产生的抗体包被外泌体相关，从而导致抗原特异性抑制其功能。因此，由游离exRNA靶向的功能细胞可以通过转染伴生细胞外泌体进行，然后将RNA货物转移到受体细胞。这与关于从多泡体释放含有rna的外泌体用于随后的细胞间靶向的经典观点形成对比。这种细胞间转移exRNA的新途径具有独特的生物学和免疫学意义，并且由于大多数人类血液中的exRNA不在外泌体中，因此可能与疾病的评估和治疗有关。
Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.1161/atvbaha.112.300139
发表时间：
2013-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Boon RA;Vickers KC
通讯作者：
Vickers KC
影响因子：
3.7
作者：
Li L;Zhu D;Huang L;Zhang J;Bian Z;Chen X;Liu Y;Zhang CY;Zen K
通讯作者：
Zen K
影响因子：
3.2
作者：
Ptak W;Nazimek K;Askenase PW;Bryniarski K
通讯作者：
Bryniarski K
血清中 microRNA 的表征：一类用于诊断癌症和其他疾病的新型生物标志物
影响因子：
44.1
作者：
Chen, Xi;Ba, Yi;Zhang, Chen-Yu
通讯作者：
Zhang, Chen-Yu