title: Dendritic cell-specific transcript: dendritic cell marker and regulator of TLR-induced cytokine production.
abstract: Dendritic cells (DCs) are the professional APCs of the immune system that dictate the type and course of an immune response. Molecular understanding of DC biology is important for the design of DC-based immunotherapies and optimal clinical applications in vaccination settings. Previously, we isolated and characterized the cDNA-encoding dendritic cell-specific transcript (DC-SCRIPT; also known as ZNF366). DC-SCRIPT mRNA expression in the immune system was confined to DCs and was reported to be an early hallmark of DC differentiation. In this study, we demonstrate IL-4 to be the dominant factor for DC-SCRIPT expression in human monocyte-derived DCs. In addition, to our knowledge, we show for the first time endogenous DC-SCRIPT protein expression in human DCs both in vitro and in situ. DC-SCRIPT protein is detected early upon differentiation of monocytes into DCs and is also present in multiple freshly isolated DC subsets. Maturation of DCs with TLR ligands further increased DC-SCRIPT mRNA expression, suggesting a role in DC maturation. Indeed, small interfering RNA-mediated knockdown of DC-SCRIPT affected the cytokine response upon TLR stimulation. These DCs displayed enhanced IL-10 and decreased IL-12 production, compared with wild-type DCs. Silencing of IL-10 in DC-SCRIPT knockdown DCs rescued IL-12 expression, suggesting a primary role for DC-SCRIPT in the regulation of IL-10 production.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Saartje
authors.initials: S
authors.lastname: Hontelez
authors.forename: Marleen
authors.initials: M
authors.lastname: Ansems
authors.forename: Nina
authors.initials: N
authors.lastname: Karthaus
authors.forename: Malou
authors.initials: M
authors.lastname: Zuidscherwoude
authors.forename: Maaike W
authors.initials: MW
authors.lastname: Looman
authors.forename: Vassilis
authors.initials: V
authors.lastname: Triantis
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology; D056004:Molecular Dynamics Simulation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; C508609:IL10 protein, human; C508598:IL4 protein, human; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C515832:ZNF366 protein, human; D016753:Interleukin-10; D015847:Interleukin-4