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Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-02-19 , DOI: 10.15252/embr.201948925
Lola Fernández-Messina 1, 2, 3 , Ana Rodríguez-Galán 1, 2 , Virginia G de Yébenes 4 , Cristina Gutiérrez-Vázquez 2 , Sandra Tenreiro 5 , Miguel C Seabra 5 , Almudena R Ramiro 4 , Francisco Sánchez-Madrid 1, 2, 3
Affiliation  

Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders.

中文翻译:

细胞外小泡微RNA的转移控制生发中心反应和抗体产生。

细胞间通讯精心策划了针对致病因子的有效免疫应答。细胞外囊泡(EVs)是细胞间通讯的有效介体。电动汽车带有生物活性分子,包括微RNA,可调节受体细胞中的基因表达和功能。在这里,我们表明同源的主要TB淋巴细胞免疫接触的形成促进了非常有限的T细胞EV-microRNA(mmu-miR20-a-5p,mmu-miR-25-3p和mmu-miR-155)的转移-3p)到B单元。转移的EV-microRNA靶向控制B细胞功能的关键基因,包括促凋亡BIM和细胞周期调节剂PTEN。在TB同源相互作用期间转移的EV-microRNA也促进存活,增殖和抗体类别转换。使用带有Rab27KO EV缺陷T细胞的小鼠嵌合体,我们证明了小EV的转移是生发中心反应和体内抗体生产所必需的,揭示了通过T细胞起源的EV-microRNA转移控制B细胞反应的机制。这些发现还提供了与Rab27a基因突变相关的Griscelli综合征的机制性见解,并可能解释了在这种发病机理以及其他免疫相关性和炎性疾病中观察到的抗体缺陷。
更新日期:2020-02-19
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