Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets.
Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets.
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DOI：
10.1038/srep20254
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发表时间：
2016-02-04
影响因子：
4.6
通讯作者：
Whiteside TL
中科院分区：
文献类型：
--
作者：
Muller L;Mitsuhashi M;Simms P;Gooding WE;Whiteside TL
肿瘤细胞来源的外来体（TEX）抑制免疫细胞的功能。在此，评估了体外暴露于外来体的原代人T淋巴细胞的基因谱的变化。从正常供体的外周血中分离CD 4 + Tconv、CD 8 + T或CD 4 + CD 39 + Treg，并与TEX或从培养的树突状细胞（DEX）的上清液中分离的外来体共孵育。通过qRT-PCR定量这些T细胞中24-27个免疫应答相关基因的表达水平。在活化的T细胞中，TEX和DEX上调多个基因的mRNA表达水平。ΔCt值的多因素数据分析确定了T细胞活化和免疫细胞类型，而不是外泌体来源，作为外泌体调节基因表达的因素。Treg对TEX介导的效应比其他T细胞亚群更敏感。在Treg中，TEX介导的调节腺苷途径的基因下调转化为CD 39的高表达和腺苷产生的增加。TEX还诱导了CD 4 + Tconv中抑制基因的上调，这导致其表面CD 69的丢失和功能下降。外泌体不被T细胞内化，但它们携带并递送至细胞表面受体的信号调节人T淋巴细胞的基因表达和功能。
Tumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were evaluated. CD4+ Tconv, CD8+ T or CD4+ CD39+ Treg were isolated from normal donors’ peripheral blood and co-incubated with TEX or exosomes isolated from supernatants of cultured dendritic cells (DEX). Expression levels of 24–27 immune response-related genes in these T cells were quantified by qRT-PCR. In activated T cells, TEX and DEX up-regulated mRNA expression levels of multiple genes. Multifactorial data analysis of ΔCt values identified T cell activation and the immune cell type, but not exosome source, as factors regulating gene expression by exosomes. Treg were more sensitive to TEX-mediated effects than other T cell subsets. In Treg, TEX-mediated down-regulation of genes regulating the adenosine pathway translated into high expression of CD39 and increased adenosine production. TEX also induced up-regulation of inhibitory genes in CD4+ Tconv, which translated into a loss of CD69 on their surface and a functional decline. Exosomes are not internalized by T cells, but signals they carry and deliver to cell surface receptors modulate gene expression and functions of human T lymphocytes.