title: DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation.
abstract: The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked. Dual-knockdown and inhibition experiments demonstrated that neither GILZ nor glucocorticoid receptor play a role in TLR-induced IL-10 production after DC-SCRIPT knockdown. The NF-κB pathway is another route involved in IL-10 production after DC activation. Strikingly, inhibition of NF-κB led to a decreased TLR-mediated IL-10 production in DC-SCRIPT knockdown DCs. Moreover, DC-SCRIPT knockdown DCs showed enhanced phosphorylation, acetylation, and IL10 enhancer binding of the NF-κB subunit p65. These data demonstrate that besides nuclear receptor regulation, DC-SCRIPT also modulates activation of NF-κBp65 after TLR activation in human DCs.
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
authors.forename: Jonas Nørskov
authors.initials: JN
authors.lastname: Søndergaard
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
authors.forename: Susanna
authors.initials: S
authors.lastname: Poghosyan
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
authors.forename: Saartje
authors.initials: S
authors.lastname: Hontelez
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Louche
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
authors.forename: Maaike W G
authors.initials: MW
authors.lastname: Looman
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: Ansems
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands Gosse.Adema@radboudumc.nl.
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D004789:Enzyme Activation; D055786:Gene Knockout Techniques; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011965:Receptors, Glucocorticoid; C404226:TSC22D3 protein, human; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D014157:Transcription Factors; C515832:ZNF366 protein, human; D016753:Interleukin-10; D050880:p300-CBP Transcription Factors