Neutralization of IL-10 Produced by B Cells Promotes Protective Immunity during Persistent HCV Infection in Humanized Mice.
Neutralization of IL-10 Produced by B Cells Promotes Protective Immunity during Persistent HCV Infection in Humanized Mice.
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中和 B 细胞产生的 IL-10 可促进人源化小鼠持续 HCV 感染期间的保护性免疫。
DOI：
10.1002/eji.201948488
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发表时间：
2020-04
影响因子：
5.4
通讯作者：
Qin Pan
中科院分区：
文献类型：
--
作者：
Min Liu;Han-Yu Chen;Liang Luo;Yaping Wang;Dongli Zhang;Neng Song;Fu-Bing Wang;Qiao Li;Xiao-Lian Zhang;Qin Pan
慢性丙型肝炎病毒（HCV）感染可导致肝硬化，并与死亡率增加有关。产生白细胞介素（IL）-10的B细胞（B10细胞）是抑制细胞免疫应答的调节细胞。在这里，我们的目的是确定HCV是否诱导B10细胞，并评估B10细胞在HCV感染过程中的作用。HCV诱导的B10细胞富集在CD 19 hi和CD 1dhi CD 5+细胞群中。HCV主要触发TLR 2-MyD 88-NF-κB和AP-1信号通路以驱动B细胞产生IL-10。在持续HCV感染的人源化鼠模型中，为了中和B10细胞产生的IL-10，用pcCD 19 scFv-IL-10 R处理小鼠，pcCD 19 scFv-IL-10 R含有编码抗CD 19单链可变片段（CD 19 scFv）和IL-10受体α链胞外结构域（sIL-10 Ra）的基因。这种治疗导致脾和肝中B10细胞的显著减少，针对HCV的细胞毒性CD 8 + T细胞应答的增加，以及感染的人源化小鼠中的低病毒载量。我们的研究结果表明，通过中和IL-10靶向B10细胞可能提供一种新的策略，以加强抗HCV免疫治疗。本文受版权保护。All rights reserved.
Chronic hepatitis C virus (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 CD19hi and CD1dhi CD5+ 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. This article is protected by copyright. All rights reserved.
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DOI：
10.4049/jimmunol.0900270
发表时间：
2009-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yanaba K;Bouaziz JD;Matsushita T;Tsubata T;Tedder TF
通讯作者：
Tedder TF
影响因子：
32.4
作者：
Yanaba, Koichi;Bouaziz, Jean-David;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.
影响因子：
8
作者：
S. Russi;A. Vincenti;A. Vinella;M. Mariggiò;F. Pavone;F. Dammacco;G. Lauletta
通讯作者：
S. Russi;A. Vincenti;A. Vinella;M. Mariggiò;F. Pavone;F. Dammacco;G. Lauletta
DOI：
10.1056/nejmra1213651
发表时间：
2013-05-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liang TJ;Ghany MG
通讯作者：
Ghany MG
影响因子：
3.2
作者：
I. Weisberg;I. Jacobson
通讯作者：
I. Weisberg;I. Jacobson