ORIGINAL RESEARCH article
Front. Immunol.
Sec. Parasite Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1620225
miR-378a-5p targeting BRAF regulates CD4 + T cells differentiation to Th1 under rEg.P29 induction
Provisionally accepted
- Ningxia Medical University, Yinchuan, China
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Cystic echinococcosis (CE) is a globally distributed zoonotic disease caused by Echinococcus granulosus (Eg) that often presents with insidious onset and asymptomatic progression. Although several Eg-based recombinant vaccines have been developed for the prevention of CE, our previous study demonstrated that recombinant Eg.P29 (rEg.P29) is a potent immunogen that induces a robust Th1 immune response. Furthermore, microarray data from miRNA profiling of CD4 + T cells isolated from mouse spleens showed that miR-378a-5p was significantly upregulated one week after immunization with rEg.P29. In this context, bioinformatics predictions and dual-luciferase reporter assays identified BRAF as a direct miR-378a-5p target, with downstream signaling involving the MAPK/ERK pathway. Our research demonstrated that rEg.P29 immunization increased miR-378a-5p expression in naïve CD4 + T cells, reduced BRAF, MEK1/2, and ERK1/2 expression, and promoted Th1 differentiation while inhibiting Th2 differentiation.Overexpression of miR-378a-5p in naïve CD4 + T cells yielded similar results, whereas knockdown of miR-378a-5p had the opposite effect. In summary, our findings reveal that under the induction of rEg.P29, miR-378a-5p targeted to BRAF regulation and initiated the differentiation of CD4+T cells in mouse spleen to Th1 direction, and MAPK/ERK pathway may be involved in this process, identifying miR-378a-5p as a potential biomarker and immunomodulatory target in CE.
Keywords: Echinococcus granulosus P29, miR-378a-5p, BRAF, CD4 + T cells differentiation, MAPK/ERK Pathway
Received: 29 Apr 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Zhang, Mu, Wang, Qian and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mingxing Zhu, Ningxia Medical University, Yinchuan, China
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