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Hepatology
Original article
Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection
Haijun Li1, Naicui Zhai1, Zhongfeng Wang2, Hongxiao Song1, Yang Yang1, An Cui1, Tianyang Li1, Guangyi Wang3, Junqi Niu2, Ian Nicholas Crispe1,4, Lishan Su1,5, Zhengkun Tu1,2
Author affiliations
Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China
Institute of Liver Diseases, The First Hospital, Jilin University, Changchun, China
Department of Liver and Gall Surgery, The First Hospital, Jilin University, Changchun, China
Department of Pathology, University of Washington, Seattle, Washington, USA
Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence to Professor Zhengkun Tu, Institute of translational medicine, The First Hospital, Jilin University, Changchun, 130061, China; [email protected]
Abstract
Background and aims HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells.
Methods Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining.
Results In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation.
Conclusions Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
http://dx.doi.org/10.1136/gutjnl-2017-314098
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发表于 2018-10-9 17:07