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Ly6Chi monocytes regulate T cell responses in viral hepatitis
Jiangao Zhu, … , Songfu Jiang, Yiping Yang
Jiangao Zhu, … , Songfu Jiang, Yiping Yang
Published October 20, 2016
Citation Information: JCI Insight. 2016;1(17):e89880. https://doi.org/10.1172/jci.insight.89880.
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Research Article Immunology Virology

Ly6Chi monocytes regulate T cell responses in viral hepatitis

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Abstract

Viral hepatitis remains a global health challenge despite recent progress in the development of more effective therapies. Although virus-specific CD8+ and CD4+ T cell responses are essential for viral clearance, it remains largely unknown what regulates T cell–mediated viral clearance. Thus, a better understanding of the regulation of anti-viral T cell immunity would be critical for the design of more effective therapies for viral hepatitis. Using a model of adenovirus-induced hepatitis, here we showed that adenoviral infection induced recruitment of Ly6Chi monocytes to the liver in a CCR2-dependent manner. These recruited Ly6Chi monocytes suppressed CD8+ and CD4+ T cell responses to adenoviral infection, leading to a delay in viral clearance. In vivo depletion of Ly6Chi monocytes markedly enhanced anti-viral T cell responses and promoted viral clearance. Mechanistically, we showed that induction of iNOS and the production of NO by Ly6Chi monocytes are critical for the suppression of T cell responses. In addition, a contact-dependent mechanism mediated by PD-1 and PD-L1 interaction is also required for T cell suppression by Ly6Chi monocytes. These findings suggest a critical role for Ly6Chi monocytes in the regulation of T cell immunity in viral hepatitis and may provide new insights into development of more effective therapies for treating viral hepatitis based on targeting the immunosuppressing monocytes.

Authors

Jiangao Zhu, Huiyao Chen, Xiaopei Huang, Songfu Jiang, Yiping Yang

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Figure 1

Recruitment of Ly6Chi monocytes and T cells to the liver upon adenoviral infection.

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Recruitment of Ly6Chi monocytes and T cells to the liver upon adenoviral...
Mice were infected with recombinant adenovirus encoding LacZ (Ad) intravenously or left uninfected (Naive). (A) Five days after infection, cells from the spleen or the liver were analyzed for the presence of Ly6Chi monocytes and Ly6G+ granulocytes by flow cytometry analysis. FACS plots are shown with the percentages of Ly6Chi monocytes (CD11b+Ly6Chi Ly6G–) and Ly6G+ granulocytes (CD11b+Ly6CloLy6G+) among CD11b+ cells indicated. (B) At 4 hours and days 1, 2, 3, 4, 5, 6, and 7 after infection, total mean numbers of Ly6Chi monocytes and Ly6G+ granulocytes ± SD in the spleen and liver tissues of Ad-infected mice are shown (n = 3 per group). (C) At day 5 after infection, cells from the spleen or liver were analyzed for the infiltration of CD4+ and CD8+ T cells. FACS plots are shown with the percentages of CD4+ and CD8+ T cells among total splenic or intrahepatic lymphocytes indicated. (D) At 4 hours and days 1, 2, 3, 4, 5, 6, and 7 after infection, total mean numbers of CD4+ and CD8+ T cells ± SEM in the spleen and liver tissues of Ad-infected mice are shown (n = 3 per group). Results are representative of 3 independent experiments.

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ISSN 2379-3708

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