AUTHOR=Du Xiancai , Zhu Mingxing , Zhang Tingrui , Wang Chan , Tao Jia , Yang Songhao , Zhu Yazhou , Zhao Wei 

TITLE=The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.773276

DOI=10.3389/fimmu.2022.773276

ISSN=1664-3224

ABSTRACT=<p><italic>Cystic echinococcosis</italic> (CE) is a zoonotic parasitic disease spread worldwide caused by <italic>Echinococcus granulosus</italic> (<italic>E</italic>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 <italic>E</italic>g are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant <italic>E</italic>g.P29 (r<italic>E</italic>g.P29) has a marvelous immunoprotection and can induce Th1 immune response. Furthermore, data of miRNA microarray in mice spleen CD4<sup>+</sup> T cells showed that miR-126a-5p was significantly elevated 1 week after immunization by using r<italic>E</italic>g.P29. Therefore, in this perspective, we discussed the role of miR-126a-5p in the differentiation of naive CD4<sup>+</sup> T cells into Th1/Th2 under r<italic>E</italic>g.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<sup>+</sup> 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<sup>+</sup> T cells into Th1 through downregulating DLK1 <italic>in vivo</italic> and <italic>in vitro</italic>. Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.</p>