Table_1_Antigen-specific downregulation of miR-150 in CD4 T cells promotes cell survival.xlsx

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but up-regulated in CD8+ T cells. CD4+ and CD8+ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4+ T cells. Transcriptome analysis of CD4+ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4+ T cells, but not in bystander CD4+ nor in CD8+ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150-/- antigen-specific CD4+ T. Thus, miR-150 impacts CD4+ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.

MicroRNA-150（miR-150）已被证实其在免疫系统中的普遍作用，然而关于其在CD4+ T细胞反应中作用的信息却鲜为人知。在针对超抗原金黄色葡萄球菌肠毒素A的T细胞反应过程中，miR-150在抗原特异性CD4+ T细胞中的表达呈现下调趋势，而在CD8+ T细胞中则上调。与野生型（WT）小鼠相比，miR-150敲除（miR-150-KO）小鼠的CD4+和CD8+ T细胞克隆扩增更为显著，但miR-150却能选择性抑制CD4+ T细胞的IL-2产生。CD4+ T细胞的转录组分析表明，在miR-150缺失的情况下，细胞凋亡和mTOR通路高度富集。机制研究证实，miR-150在抗原特异性CD4+ T细胞中特异性地促进细胞凋亡，而对旁观者CD4+ T细胞及CD8+ T细胞则无此作用。此外，抑制与mTOR相关的线粒体超氧化物歧化酶-2可增加miR-150-/-抗原特异性CD4+ T细胞中的细胞凋亡。因此，miR-150通过减轻IL-2的产生以及克隆扩增，影响CD4+ T细胞的辅助活性，并抑制超氧化物歧化酶以促进细胞凋亡。