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

• Published in: Frontiers in immunology Vol. 13; p. 773276
• Main Authors: Du, Xiancai, Zhu, Mingxing, Zhang, Tingrui, Wang, Chan, Tao, Jia, Yang, Songhao, Zhu, Yazhou, Zhao, Wei
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 08.02.2022
• Subjects: CD4+ T cells; DLK1; Immunology; miR-126a-5p; Notch1; rEg.P29; Th1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.773276

Cystic echinococcosis (CE) is a zoonotic parasitic disease spread worldwide caused by Echinococcus granulosus ( E 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 E g are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant E g.P29 (r E g.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 r E g.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 r E 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 + 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 in vivo and in vitro . Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.