title: Interleukin 23 produced by myeloid dendritic cells contributes to T-cell dysfunction in HIV type 1 infection by inducing SOCS1 expression.
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.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of California-San Diego, La Jolla.
authors.forename: Ankita
authors.initials: A
authors.lastname: Garg
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of California-San Diego, La Jolla.
authors.forename: Pratima
authors.initials: P
authors.lastname: Rawat
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of California-San Diego, La Jolla Rady Children's Hospital, San Diego, California.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D053759:Interleukin-23 / Q000378:metabolism*; D008297:Male; D009975:Orthomyxoviridae / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D053759:Interleukin-23; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma
keywords: HIV-1; IL-23; SOCS1; gp120; myeloid dendritic cells