title: Protein kinase CK2 controls T-cell polarization through dendritic cell activation in response to contact sensitizers.
abstract: Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin disease caused by chemicals present in the daily or professional environment. NiSO4and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These contact sensitizers are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs; professional APCs), leading to the generation of CD8+Tc1/Tc17 and CD4+Th1/Th17 effector T cells. In the present study, using a peptide array approach, we identified protein kinase CK2 as a novel kinase involved in the activation of human monocyte-derived DCs (MoDCs) in response to NiSO4and DNCB. Inhibition of CK2 activity in MoDCs led to an altered mature phenotype with lower expression of CD54, PDL-1, CD86, and CD40 in response to NiSO4or DNCB. CK2 activity also regulated proinflammatory cytokine production, such as TNF-α, IL-1β, and IL-23 in MoDCs. Moreover, in a DC/T cell coculture model in an allogeneic setup, CK2 activity in MoDCs played a major role in Th1 polarization in response to NiSO4and DNCB. CK2 inhibition in MoDCs led to an enhanced Th2 polarization in the absence of contact sensitizer stimulation.
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Marie
authors.initials: M
authors.lastname: de Bourayne
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Yann
authors.initials: Y
authors.lastname: Gallais
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Zeina
authors.initials: Z
authors.lastname: El Ali
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousseau
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Damiens
authors.affiliation: Cancer and Infection Biology, UMR1036, INSERM, Institute of Life Sciences Research and Technology (iRTSV), Atomic Energy and Alternative Energy Commission (CEA), Grenoble, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Cochet
authors.affiliation: Cancer and Infection Biology, UMR1036, INSERM, Institute of Life Sciences Research and Technology (iRTSV), Atomic Energy and Alternative Energy Commission (CEA), Grenoble, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Filhol
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: UMR996, Inflammation, Chemokines, and Immunopathology, INSERM, University Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; and saadia.kerdine-romer@u-psud.fr.
authors.forename: Saadia
authors.initials: S
authors.lastname: Kerdine-Römer
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D047390:Casein Kinase II / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D003911:Dextrans / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009287:Naphthyridines / Q000494:pharmacology; D009532:Nickel / Q000633:toxicity*; D010619:Phenazines; D020543:Proteome / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D003911:Dextrans; D004137:Dinitrochlorobenzene; D009287:Naphthyridines; D010619:Phenazines; D020543:Proteome; D012333:RNA, Messenger; D014157:Transcription Factors; C015219:fluorescein isothiocyanate dextran; C029938:nickel sulfate; D009532:Nickel; C555142:silmitasertib; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; D016650:Fluorescein-5-isothiocyanate
keywords: Th1/Th2/Th17 cell; allergic contact dermatitis; cytokine; dendritic cell; protein kinase