干扰素-α治疗期间诱导的免疫调节损害通过CD24 + CD38 hi B细胞

StephenW

Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24 + CD38 hi B Cells
Binqing Fu  1   2 , Dongyao Wang  1   2 , Xiaokun Shen  1   2 , Chuang Guo  1   2 , Yanyan Liu  3 , Ying Ye  3 , Rui Sun  1   2 , Jiabin Li  3 , Zhigang Tian  1   2 , Haiming Wei  1   2
Affiliations
Affiliations

    1
    Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China.
    2
    Institute of Immunology, University of Science and Technology of China, Hefei, China.
    3
    Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

    PMID: 33424840 PMCID: PMC7786281 DOI: 10.3389/fimmu.2020.591269

Abstract

Type I interferon is widely used for antiviral therapy, yet has yielded disappointing results toward chronic HBV infection. Here we identify that PEG-IFNα-2b therapy toward persistent infection in humans is a double-edged sword of both immunostimulation and immunomodulation. Our studies of this randomised trial showed persistent PEG-IFNα-2b therapy induced large number of CD24+CD38hi B cells and launched a CD24+CD38hi B cells centered immunosuppressive response, including downregulating functions of T cells and NK cells. Patients with low induced CD24+CD38hi B cells have achieved an improved therapeutic effect. Specifically, using the anti-CD24 antibody to deplete CD24+CD38hi B cells without harming other B cell subsets suggest a promising strategy to improve the therapeutic effects. Our findings show that PEG-IFNα-2b therapy toward persistent infection constitutes an immunomodulation effect, and strategies to identifying the molecular basis for the antiviral versus immunomodulatory effects of PEG-IFNα-2b to selectively manipulate these opposing activities provide an opportunity to ameliorate anti-virus immunity and control viral infection.

Keywords: CD24+CD38hi B; Peg-IFNα-2b; anti-virus function; chronic hepatitis B virus infection; immunomodulatory effects.

Copyright © 2020 Fu, Wang, Shen, Guo, Liu, Ye, Sun, Li, Tian and Wei.

StephenW

干扰素-α治疗期间诱导的免疫调节损害通过CD24 + CD38 hi B细胞的抗HBV免疫反应
傅彬清1 2，王东耀1 2，沉晓坤1 2，创国1 2，刘彦彦3，叶烨3，孙瑞1 2，李佳斌3，田志刚1 2，魏海明1 2
隶属关系
隶属关系

    1个
    中国科学技术大学生命科学学院，合肥微尺度国家科学实验室分子医学系，中国科学院先天免疫与慢性疾病重点实验室，中国合肥。
    2
    中国科学技术大学免疫学研究所，合肥
    3
    安徽医科大学附属第一医院感染科，安徽合肥

    PMID：33424840 PMCID：PMC7786281 DOI：10.3389 / fimmu.2020.591269

抽象

I型干扰素已广泛用于抗病毒治疗，但对慢性HBV感染却产生令人失望的结果。在这里，我们确定针对人类持续感染的PEG-IFNα-2b治疗是免疫刺激和免疫调节的双刃剑。我们对该随机试验的研究表明，持续的PEG-IFNα-2b治疗可诱导大量CD24 + CD38hi B细胞并启动以CD24 + CD38hi B细胞为中心的免疫抑制反应，包括下调T细胞和NK细胞的功能。具有低诱导的CD24 + CD38hi B细胞的患者获得了改善的治疗效果。具体而言，使用抗CD24抗体消耗CD24 + CD38hi B细胞而又不损害其他B细胞亚群提示了改善治疗效果的有前途的策略。我们的研究结果表明，针对持续感染的PEG-IFNα-2b治疗具有免疫调节作用，而确定PEG-IFNα-2b的抗病毒与免疫调节作用的分子基础以选择性操纵这些相反活性的策略提供了改善抗病毒免疫力和控制病毒感染。

关键字：CD24 + CD38hi B; Peg-IFNα-2b；防病毒功能；慢性乙型肝炎病毒感染；免疫调节作用。

版权所有©2020 Fu，Wang，Shen，Guo，Liu，Ye，Sun，Li，Tian和Wei。

StephenW

https://www.frontiersin.org/arti ... mmu.2020.591269/pdf