Interleukin 23 produced by myeloid dendritic cells contributes to T-cell dysfunction in HIV type 1 infection by inducing SOCS1 expression

J Infect Dis. 2015 Mar 1;211(5):755-68. doi: 10.1093/infdis/jiu523. Epub 2014 Sep 18.


The mechanism of myeloid dendritic cell (mDC)-mediated impaired T-cell function was investigated during human immunodeficiency virus type 1 (HIV-1) infection. HIV or gp120 were found to inhibit lipopolysaccharide-induced mDC maturation and cause defects in allogeneic T-cell proliferation, interleukin 2 and interferon γ (IFN-γ) production, and phosphorylated STAT1 expression. gp120-treated mDCs downregulated autologous T-cell proliferation and IFN-γ production against a peptide pool consisting of cytomegalovirus, Epstein-Barr virus, and influenza virus (CEF). These T-cell defects were associated with a decrease in production of the T-helper type 1-polarizing cytokine interleukin 12p70 and an increase in interleukin 23 (IL-23) production by gp120-treated mDCs. gp120-induced IL-23 upregulated suppressor of cytokine signaling 1 (SOCS1) protein in T cells, which inhibited IFN-γ production and killing of CEF-pulsed monocytes. These effector functions were recovered by silencing SOCS1 in T cells. Furthermore, we observed IL-23-induced SOCS1 binding to the IFN-γ transcription complex. These results identify SOCS1 as a novel target to improve the immune function in HIV-infected persons.

Keywords: HIV-1; IL-23; SOCS1; gp120; myeloid dendritic cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytomegalovirus / immunology
  • Dendritic Cells / immunology*
  • Female
  • Gene Expression
  • HIV Infections / immunology*
  • HIV-1
  • Herpesvirus 4, Human / immunology
  • Humans
  • Interferon-gamma / antagonists & inhibitors*
  • Interleukin-23 / metabolism*
  • Male
  • Orthomyxoviridae / immunology
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / biosynthesis*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Young Adult


  • Interleukin-23
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interferon-gamma