Regulation of Host Regulatory T Cell Differentiation by emu-let-7-5p in Echinococcus multilocularis Infection Through Targeting NFκB2

文献类型： 外文期刊

第一作者： Wang, Liqun

作者： Wang, Liqun;Wu, Keke;Li, Li;Amuda, Tharheer Oluwashola;Wu, Yixuan;Pu, Guiting;Liu, Tingli;Cao, Shanling;Yin, Hong;Fu, Baoquan;Yan, Hongbin;Luo, Xuenong;Yin, Hong;Fu, Baoquan;Luo, Xuenong;Yan, Hongbin

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关键词： E. multilocularis; emu-let-7-5p; NF kappa B2; Treg cell differentiation

期刊名称：FASEB JOURNAL （ 影响因子：4.2； 五年影响因子：4.5 ）

ISSN： 0892-6638

年卷期： 2025 年 39 卷 9 期

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收录情况： SCI

摘要： Regulatory T cells (Treg) play a crucial role in creating an immunosuppressive microenvironment surrounding the metacestode during chronic alveolar echinococcosis (AE). However, the mechanisms by which E. multilocularis induces Treg differentiation, particularly the role of parasite-derived microRNAs (miRNAs), remain largely unexplored. Here, we demonstrate that E. multilocularis can significantly induce the differentiation of Treg in mice. Emu-let-7-5p is upregulated in peripheral blood lymphocyte cells (PBLC) and splenic lymphocytes of E. multilocularis-infected mice. Exosomes enriched with emu-let-7-5p were found to upregulate the expressions of Treg markers. Conversely, exosomes collected following the knockdown of worm-derived emu-let-7-5p via RNA interference resulted in a reversal of Treg marker expression in PBLC. Mechanistically, emu-let-7-5p regulates Treg differentiation by targeting NF kappa B2. Knockdown of emu-let-7-5p in E. multilocularis-infected mice resulted in diminished Treg differentiation, leading to a significant reduction in worm load. These findings reveal that emu-let-7-5p drives Treg differentiation by suppressing NF kappa B2, representing a novel immune evasion strategy of E. multilocularis. Sustained inhibition of parasite-derived emu-let-7-5p may provide a therapeutic avenue for controlling AE progression.

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