Non-specific immune responses to antigens have been demonstrated as being enhanced during chronic hepatitis B virus (HBV) infection. Here, we evaluated the role of interleukin-10 (IL-10)-producing regulatory B-cells (Bregs) in the pathogenesis of HBV-related liver fibrosis (HBV-LF) and assessed their immunoregulatory effects. Sixty-seven patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. Numbers and frequencies of peripheral B-cells (memory CD19+CD24hiCD27+ cells, immature/transitional CD19+CD24hiCD38hi cells, mature CD19+CD24intCD38int cells) were tested and analysed. Flow cytometry-sorted CD4+T cells were cultured with autologous Bregs to elucidate the effects of Bregs on CD4+T cells, including effector T and regulatory T-cells (Tregs). The potential immunoregulatory mechanism of Bregs was also investigated. The numbers of total B-cells and Bregs were enriched in CHB patients. The frequency of Bregs was negatively correlated with elevated alanine aminotransferase (ALT) and histological inflammation grades (G), but positively correlated with advanced histological fibrosis stages (S) and enhanced HBV replication. The phenotype of Bregs was predominantly characterized as CD19+CD24hiCD38hi. In co-culture with Bregs, CD4+CD25−T cells from CHB patients produced less interferon-γ (IFN-γ) and IL-17 but more IL-4 than CD4+CD25−T cells alone, whereas their conversions into Tregs and IL-10+T cells were enhanced. In addition, Breg depletion in CHB samples dramatically decreased Treg numbers and expression of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), IL-10 and transforming growth factor-β (TGF-β). Moreover, the observed regulatory effect was partly dependent on IL-10 release and cell-to-cell contact. Elevated Bregs can suppress effector T but enhance Treg functions, which might influence immune tolerance in chronic HBV infection.
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Mitochondrial protein quality control plays a decisive role in the maintenance of a proper mitochondrial function in metabolically active tissues such as skeletal muscle. Several chaperones and proteases, involved in the regulation of mitochondrial protein quality control, are altered in obesity and type 2 diabetes mellitus. For further details see Dahlmans et al. pp. 843–852.
Research Article|
April 29 2016
IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection
Yun Liu;
Yun Liu
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Li-sha Cheng;
Li-sha Cheng
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Sheng-di Wu;
Sheng-di Wu
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Si-qi Wang;
Si-qi Wang
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Lei Li;
Lei Li
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Wei-min She;
Wei-min She
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Jing Li;
Jing Li
†Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai 200065, China
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Ji-yao Wang;
Ji-yao Wang
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Wei Jiang
*Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Correspondence: Wei Jiang (email [email protected]).
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Publisher: Portland Press Ltd
Received:
September 14 2015
Revision Received:
March 11 2016
Accepted:
March 15 2016
Accepted Manuscript online:
March 15 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (11): 907–919.
Article history
Received:
September 14 2015
Revision Received:
March 11 2016
Accepted:
March 15 2016
Accepted Manuscript online:
March 15 2016
Citation
Yun Liu, Li-sha Cheng, Sheng-di Wu, Si-qi Wang, Lei Li, Wei-min She, Jing Li, Ji-yao Wang, Wei Jiang; IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection. Clin Sci (Lond) 1 June 2016; 130 (11): 907–919. doi: https://doi.org/10.1042/CS20160069
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