title: Decreased interferon-α production in response to CpG DNA dysregulates cytokine responses in patients with multiple sclerosis.
abstract: Type I interferons (IFNs), represented by IFN-α and β, activate immune effector cells belonging to the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDCs) produce IFN-α in response to CpG DNA. We aimed to examine the impact of pDC-produced IFN-α on the adaptive immune system in Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-α production was significantly decreased in PBMCs from MS patients. Decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were found in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In samples pre-treated with IFN-α and IFN-β, decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were detected in PBMCs from MS patients. These results suggest that CpG DNA-induced decreased IFN-α production causes pro-inflammatory cytokine secretion, and either IFN-α or IFN-β induces anti-inflammatory cytokine secretion in the adaptive immune system in MS.
authors.affiliation: Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. hirotani@med.hokudai.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirotani
authors.forename: Masaaki
authors.initials: M
authors.lastname: Niino
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yaguchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D018899:CpG Islands; D016207:Cytokines / Q000276:immunology*; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; D004247:DNA