Diabetes Center and the Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2012;7(5):e36684. doi: 10.1371/journal.pone.0036684. Epub 2012 May 18.
MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD) mice with a genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a expression than C57BL/6J autoimmune resistant mice. Inhibition of miR-10a expression in vitro leads to reduced FoxP3 expression levels and miR-10a expression is lower in unstable "exFoxP3" T cells. Unstable in vitro TGF-ß-induced, iTregs do not express miR-10a unless cultured in the presence of retinoic acid (RA) which has been associated with increased stability of iTreg, suggesting that miR-10a might play a role in stabilizing Treg. However, genetic ablation of miR-10a neither affected the number and phenotype of natural Treg nor the capacity of conventional T cells to induce FoxP3 in response to TGFβ, RA, or a combination of the two. Thus, miR-10a is selectively expressed in Treg but inhibition by antagomiRs or genetic ablation resulted in discordant effects on FoxP3.
微小 RNA（miRNA）对于调节性 T 细胞（Treg）的稳定性和功能至关重要。我们报告说，miRNA-10a（miR-10a）在 Treg 中表达，但不在其他 T 细胞中表达，包括个别胸腺细胞亚群。在近交系小鼠品系中的表达谱分析表明，具有自身免疫性糖尿病遗传易感性的非肥胖型糖尿病（NOD）小鼠比 C57BL/6J 自身免疫性抗性小鼠具有更低的 Treg 特异性 miR-10a 表达。体外抑制 miR-10a 表达会导致 FoxP3 表达水平降低，并且不稳定的“exFoxP3”T 细胞中 miR-10a 的表达水平较低。不稳定的体外 TGF-β诱导的 iTreg 除非在维甲酸（RA）存在下培养，否则不表达 miR-10a，RA 与 iTreg 的稳定性增加有关，这表明 miR-10a 可能在稳定 Treg 中发挥作用。然而，miR-10a 的基因缺失既不影响天然 Treg 的数量和表型，也不影响常规 T 细胞响应 TGFβ、RA 或两者组合诱导 FoxP3 的能力。因此，miR-10a 选择性地在 Treg 中表达，但抗 miR-10a 或基因缺失的抑制作用导致 FoxP3 的不一致影响。
