Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells

Binqing Fu; Binqing Fu; Dongyao Wang; Dongyao Wang; Xiaokun Shen; Xiaokun Shen; Chuang Guo; Chuang Guo; Yanyan Liu; Ying Ye; Rui Sun; Rui Sun; Jiabin Li; Zhigang Tian; Zhigang Tian; Haiming Wei; Haiming Wei

doi:10.3389/fimmu.2020.591269

Frontiers in Immunology (Dec 2020)

Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells

Binqing Fu,
Binqing Fu,
Dongyao Wang,
Dongyao Wang,
Xiaokun Shen,
Xiaokun Shen,
Chuang Guo,
Chuang Guo,
Yanyan Liu,
Ying Ye,
Rui Sun,
Rui Sun,
Jiabin Li,
Zhigang Tian,
Zhigang Tian,
Haiming Wei,
Haiming Wei

Affiliations

Binqing Fu: 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
Binqing Fu: Institute of Immunology, University of Science and Technology of China, Hefei, China
Dongyao Wang: 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
Dongyao Wang: Institute of Immunology, University of Science and Technology of China, Hefei, China
Xiaokun Shen: 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
Xiaokun Shen: Institute of Immunology, University of Science and Technology of China, Hefei, China
Chuang Guo: 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
Chuang Guo: Institute of Immunology, University of Science and Technology of China, Hefei, China
Yanyan Liu: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Ying Ye: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Rui Sun: 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
Rui Sun: Institute of Immunology, University of Science and Technology of China, Hefei, China
Jiabin Li: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Zhigang Tian: 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
Zhigang Tian: Institute of Immunology, University of Science and Technology of China, Hefei, China
Haiming Wei: 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
Haiming Wei: Institute of Immunology, University of Science and Technology of China, Hefei, China

DOI: https://doi.org/10.3389/fimmu.2020.591269
Journal volume & issue: Vol. 11

Abstract

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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.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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