title: Altered molecular expression of TLR-signaling pathways affects the steady-state release of IL-12p70 and IFN-α in patients with relapsing-remitting multiple sclerosis.
abstract: Recent evidence suggests a key role of dendritic cells (DC) in the immunopathogenesis of multiple sclerosis (MS). Whereas dysfunction of DC was reported in MS patients, the underlying cause for this is not fully elucidated yet. The aim of the present study was to compare the gene expression profile of molecules involved in TLR4 and TLR7 signaling in DC from patients with MS and healthy controls. For this, circulating DC subsets were purified from patients with relapsing-remitting MS (RRMS) and from healthy controls for quantitative real-time PCR analysis. Additionally, TLR responsiveness in peripheral blood was investigated. We observed an aberrant steady-state release of IL-12p70 and IFN-α in patients with RRMS compared with healthy controls. Expression of IRF1 and JUN was reduced in conventional DC from patients with RRMS. In plasmacytoid DC from patients with RRMS, expression of IRF7 and IFNGR1 was reduced, while higher expression levels of TLR4 and LY86 were found compared with DC from healthy controls. The observed alterations in the gene expression of molecules involved in the TLR4 and TLR7 signaling pathways in circulating DC subsets may underlie the impaired IL-12p70 and IFN-α secretion in patients with RRMS, thereby potentially contributing to the disease pathogenesis of MS.
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Deckx
authors.affiliation: Department of Neurology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Willekens
authors.affiliation: REVAL Rehabilitation Research Centre, BIOMED Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Inez
authors.initials: I
authors.lastname: Wens
authors.affiliation: REVAL Rehabilitation Research Centre, BIOMED Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Bert O
authors.initials: BO
authors.lastname: Eijnde
authors.affiliation: Laboratory of Medical Microbiology, Vaccine & Infectious Diseases Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Edegem, Belgium nathalie.cools@uza.be.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
mesh_terms: D000328:Adult; D001530:Belgium; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D050856:Interferon Regulatory Factor-1; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D018664:Interleukin-12; D017471:Receptors, Interferon; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D000096743:Interferon gamma Receptor; C494257:IRF1 protein, human; C494234:IRF7 protein, human; C495345:TLR4 protein, human; C495348:TLR7 protein, human
keywords: Dendritic cells; TLR4; TLR7; innate immunity; multiple sclerosis