School of Basic Medical Science of Ningxia Medical University, Yinchuan, China.
Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, Yinchuan, China.
Front Immunol. 2022 Feb 8;13:773276. doi: 10.3389/fimmu.2022.773276. eCollection 2022.
(CE) is a zoonotic parasitic disease spread worldwide caused by (g), which sometimes causes serious damage; however, in many cases, people are not aware that they are infected. A number of recombinant vaccines based on g are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant g.P29 (rg.P29) has a marvelous immunoprotection and can induce Th1 immune response. Furthermore, data of miRNA microarray in mice spleen CD4 T cells showed that miR-126a-5p was significantly elevated 1 week after immunization by using rg.P29. Therefore, in this perspective, we discussed the role of miR-126a-5p in the differentiation of naive CD4 T cells into Th1/Th2 under rg.P29 immunization and determined the mechanisms associated with delta-like 1 homolog (DLK1) and Notch1 signaling pathway. One week after P29 immunization of mice, we found that miR-126a-5p was significantly increased and DLK1 expression was decreased, while Notch1 pathway activation was enhanced and Th1 response was significantly stronger. The identical conclusion was obtained by overexpression of mmu-miR-126a-5p in primary naive CD4 T cells in mice. Intriguingly, mmu-miR-126a-5p was significantly raised in serum from mice infected with protoscolex in the early stages of infection and markedly declined in the late stages of infection, while has-miR-126-5p expression was dramatically reduced in serum from CE patients. Taken together, we show that miR-126a-5p functions as a positive regulator of Notch1-mediated differentiation of CD4 T cells into Th1 through downregulating DLK1 and . Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.
（CE）是一种全球性的人畜共患寄生虫病，由 （g）引起，有时会造成严重损害；然而，在许多情况下，人们并不知道自己已经感染。一些基于 g 的重组疫苗被用于评估其对感染的有效性。我们之前的报告表明，重组 g.P29（rg.P29）具有极好的免疫保护作用，并能诱导 Th1 免疫反应。此外，小鼠脾脏 CD4 T 细胞 miRNA 微阵列的数据显示，rg.P29 免疫后 1 周，miR-126a-5p 显著升高。因此，从这个角度来看，我们讨论了 miR-126a-5p 在 rg.P29 免疫下，幼稚 CD4 T 细胞分化为 Th1/Th2 中的作用，并确定了与 delta-like 1 同源物（DLK1）和 Notch1 信号通路相关的机制。在小鼠 P29 免疫后 1 周，我们发现 miR-126a-5p 显著增加，DLK1 表达减少，而 Notch1 通路激活增强，Th1 反应明显增强。在小鼠原代幼稚 CD4 T 细胞中过表达 mmu-miR-126a-5p 也得到了相同的结论。有趣的是，在感染早期阶段，感染原头节的小鼠血清中 mmu-miR-126a-5p 显著升高，在感染晚期阶段则显著下降，而 CE 患者血清中 has-miR-126-5p 的表达则显著降低。总之，我们表明 miR-126a-5p 通过下调 DLK1 和 ，作为 Notch1 介导的 CD4 T 细胞向 Th1 分化的正调节剂发挥作用。hsa-miR-126-5p 可能是 CE 非常有前途的诊断生物标志物。
