Chronic HCV infection can lead to cirrhosis and is associated with increased mortality. Interleukin (IL)‐10‐producing B cells (B10 cells) are regulatory cells that suppress cellular immune responses. Here, we aimed to determine whether HCV induces B10 cells and assess the roles of the B10 cells during HCV infection. HCV‐induced B10 cells were enriched in CD19^hi and CD1d^hiCD5⁺ cell populations. HCV predominantly triggered the TLR2‐MyD88‐NF‐κB and AP‐1 signaling pathways to drive IL‐10 production by B cells. In a humanized murine model of persistent HCV infection, to neutralize IL‐10 produced by B10 cells, mice were treated with pcCD19scFv‐IL‐10R, which contains the genes coding the anti‐CD19 single‐chain variable fragment (CD19scFv) and the extracellular domain of IL‐10 receptor alpha chain (sIL‐10Ra). This treatment resulted in significant reduction of B10 cells in spleen and liver, increase of cytotoxic CD8⁺ T‐cell responses against HCV, and low viral loads in infected humanized mice. Our results indicate that targeting B10 cells via neutralization of IL‐10 may offer a novel strategy to enhance anti‐HCV immunotherapy.

中文翻译：

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B细胞产生的IL-10的中和促进了人源化小鼠持续HCV感染期间的保护性免疫。

慢性HCV感染可导致肝硬化，并伴有死亡率增加。产生白介素（IL）-10的B细胞（B10细胞）是抑制细胞免疫反应的调节细胞。在这里，我们旨在确定HCV是否诱导B10细胞并评估HCV感染期间B10细胞的作用。HCV诱导的B10细胞富含CD19 ^hi和CD1d ^hi CD5 ⁺细胞群体。HCV主要触发TLR2-MyD88-NF-κB和AP-1信号通路来驱动B细胞产生IL-10。在持续性HCV感染的人源化小鼠模型中，为了中和B10细胞产生的IL-10，对小鼠进行了pcCD19scFv-IL-10R的治疗，其中包含编码抗CD19单链可变片段（CD19scFv）和细胞外的基因IL-10受体α链（sIL-10Ra）的结构域。这种治疗导致脾脏和肝脏中B10细胞的大量减少，针对HCV的细胞毒性CD8 ⁺ T细胞反应的增加以及感染的人源化小鼠的病毒载量低。我们的结果表明，通过中和IL-10靶向B10细胞可能提供增强抗HCV免疫疗法的新策略。