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

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

Author information

1
Department of Pediatrics, Division of Infectious Diseases, University of California-San Diego, La Jolla.
2
Department of Pediatrics, Division of Infectious Diseases, University of California-San Diego, La Jolla Rady Children's Hospital, San Diego, California.

Abstract

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

PMID:
25234720
PMCID:
PMC4402373
DOI:
10.1093/infdis/jiu523
[Indexed for MEDLINE]
Free PMC Article

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