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自然杀伤 (NK) 细胞衍生的细胞外囊泡转导的 microRNAs 调控 T 细胞反应。

Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses.

机构信息

Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.

Intercellular Communication in the Inflammatory Response. Vascular Pathophysiology Area, National Center for Cardiovascular Research (CNIC), Madrid, Spain.

出版信息

Elife. 2022 Jul 29;11:e76319. doi: 10.7554/eLife.76319.

DOI:10.7554/eLife.76319
PMID:35904241
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9366747/
Abstract

Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of mRNA in CD4 T cells and subsequent de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.

摘要

自然杀伤 (NK) 细胞识别并杀死发生不同类型应激的靶细胞。NK 细胞还能够调节免疫反应。特别是，它们调节 T 细胞功能。对静息和激活的人 NK 细胞及其分泌的细胞外囊泡 (EV) 进行的小 RNA 下一代测序，导致鉴定出 NK-EV 相关 microRNAs 及其转录后修饰特征的特定组合。几种 NK-EV 的 microRNAs，即 miR-10b-5p、miR-92a-3p 和 miR-155-5p，专门针对参与 Th1 反应的分子。NK-EVs 促进 CD4 T 细胞中 mRNA 的下调，随后的去抑制导致 Th1 极化和 IFN-γ 和 IL-2 的产生。NK-EVs 对单核细胞和 moDC（单核细胞衍生的树突状细胞）的功能也有影响，促使它们激活并增加呈递和共刺激功能。纳米颗粒递送的 NK-EV microRNAs 部分再现了 NK-EV 在小鼠中的作用。我们的结果提供了关于 NK-EV 的免疫调节作用的新见解，这可能有助于改善它们作为免疫治疗工具的应用。

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