title: Ly6Chimonocytes regulate T cell responses in viral hepatitis.
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 Ly6Chimonocytes to the liver in a CCR2-dependent manner. These recruited Ly6Chimonocytes suppressed CD8+and CD4+T cell responses to adenoviral infection, leading to a delay in viral clearance. In vivo depletion of Ly6Chimonocytes markedly enhanced anti-viral T cell responses and promoted viral clearance. Mechanistically, we showed that induction of iNOS and the production of NO by Ly6Chimonocytes 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 Ly6Chimonocytes. These findings suggest a critical role for Ly6Chimonocytes 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: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, and.
authors: Jiangao
authors: J
authors: Zhu
authors: Department of Hematology,First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Huiyao
authors: H
authors: Chen
authors: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, and.
authors: Xiaopei
authors: X
authors: Huang
authors: Department of Hematology,First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Songfu
authors: S
authors: Jiang
authors: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, and.|Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors: Yiping
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D054390:Receptors, CCR2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C515335:Ccr2 protein, mouse; C498919:Cd274 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D054390:Receptors, CCR2; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse