Type 1 interferon-induced IL-7 maintains CD8 + T-cell responses and homeostasis by suppressing PD-1 expression in viral hepatitis

Lifei Hou, Zuliang Jie, Yuejin Liang, Mayura Desai, Lynn Soong, Jiaren Sun

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Type 1 interferon (IFN-I) promotes antigen-presenting cell maturation and was recently shown to induce hepatic IL-7 production during infection. Herein, we further explored the underlying mechanisms used by IFN-I to orchestrate antiviral immune responses in the liver. Acute viral hepatitis was induced by i.v. injection of adenovirus (Ad) in IFN-α receptor knockout (IFNAR -/-) and control mice. To disrupt signaling, monoclonal antibodies (mAbs) against IL-7 receptor alpha (IL-7Rα) or PD-L1 were i.p. injected. We found that CD8 + T cells in IFNAR -/- mice were less effective than those in control mice. The reduced T-cell function was accompanied by increased levels of PD-1 expression, apoptosis and decreased IFN-γ production. The lack of IFN-I signaling also impaired the expression of accessory molecules in both intrahepatic dendritic cell (DCs) and hepatocytes. PD-L1 was comparably and highly expressed on hepatocytes in both IFNAR -/- and control mice. Injection of PD-L1-specific mAb in IFNAR -/- mice reversed the compromised immune responses in the liver. Further investigation showed that hepatic IL-7 elevation was less pronounced in IFNAR -/- mice compared to the controls. A treatment with recombinant IL-7 suppressed PD-1 expression on CD8 + T cells in vitro. Accordingly, blocking IL-7R signaling in vivo resulted in increased PD-1 expression on CD8 + T cells in Ad-infected mice. Collectively, the results suggest that IFN-I-induced hepatic IL-7 production maintains antiviral CD8 + T-cell responses and homeostasis by suppressing PD-1 expression in acute viral hepatitis.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalCellular and Molecular Immunology
Volume12
Issue number2
DOIs
StatePublished - Mar 1 2015

Keywords

  • CD8 T cell
  • PD-1
  • interleukin-7
  • type 1 interferon
  • viral hepatitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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