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 <sup>-/-</sup>) 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 <sup>+</sup> T cells in IFNAR <sup>-/-</sup> 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 <sup>-/-</sup> and control mice. Injection of PD-L1-specific mAb in IFNAR <sup>-/-</sup> mice reversed the compromised immune responses in the liver. Further investigation showed that hepatic IL-7 elevation was less pronounced in IFNAR <sup>-/-</sup> mice compared to the controls. A treatment with recombinant IL-7 suppressed PD-1 expression on CD8 <sup>+</sup> T cells in vitro. Accordingly, blocking IL-7R signaling in vivo resulted in increased PD-1 expression on CD8 <sup>+</sup> T cells in Ad-infected mice. Collectively, the results suggest that IFN-I-induced hepatic IL-7 production maintains antiviral CD8 <sup>+</sup> T-cell responses and homeostasis by suppressing PD-1 expression in acute viral hepatitis.
Original language | English (US) |
---|---|
Pages (from-to) | 213-221 |
Number of pages | 9 |
Journal | Cellular and Molecular Immunology |
Volume | 12 |
Issue number | 2 |
DOIs | |
State | Published - Mar 1 2015 |
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Keywords
- CD8<sup>+</sup> T cell
- interleukin-7
- PD-1
- type 1 interferon
- viral hepatitis
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
Type 1 interferon-induced IL-7 maintains CD8 <sup>+</sup> T-cell responses and homeostasis by suppressing PD-1 expression in viral hepatitis. / Hou, Lifei; Jie, Zuliang; Liang, Yuejin; Desai, Mayura; Soong, Lynn; Sun, Jiaren.
In: Cellular and Molecular Immunology, Vol. 12, No. 2, 01.03.2015, p. 213-221.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Type 1 interferon-induced IL-7 maintains CD8 + T-cell responses and homeostasis by suppressing PD-1 expression in viral hepatitis
AU - Hou, Lifei
AU - Jie, Zuliang
AU - Liang, Yuejin
AU - Desai, Mayura
AU - Soong, Lynn
AU - Sun, Jiaren
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - CD8<sup>+</sup> T cell
KW - interleukin-7
KW - PD-1
KW - type 1 interferon
KW - viral hepatitis
UR - http://www.scopus.com/inward/record.url?scp=84938587400&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938587400&partnerID=8YFLogxK
U2 - 10.1038/cmi.2014.49
DO - 10.1038/cmi.2014.49
M3 - Article
C2 - 25027969
AN - SCOPUS:84938587400
VL - 12
SP - 213
EP - 221
JO - Cellular and Molecular Immunology
JF - Cellular and Molecular Immunology
SN - 1672-7681
IS - 2
ER -