Ly6Chi monocytes regulate T cell responses in viral hepatitis.

Published

Journal Article

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.

Full Text

Cited Authors

  • Zhu, J; Chen, H; Huang, X; Jiang, S; Yang, Y

Published Date

  • October 20, 2016

Published In

Volume / Issue

  • 1 / 17

Start / End Page

  • e89880 -

PubMed ID

  • 27777980

Pubmed Central ID

  • 27777980

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

International Standard Serial Number (ISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.89880

Language

  • eng