title: Differential activity of type I interferon subtypes for dendritic cell differentiation.
abstract: The type I interferon (IFN) family comprises 15 cytokines (in human 13α, 1β, 1ω), which exert several cellular functions through binding to a common receptor. Despite initial activation of the same Jak/Stat signalling pathway, the cellular response may differ depending on type I IFN subtype. We investigated the activity of six type I IFN subtypes - IFNα1, α2, α8, α21, ω and β- to promote the differentiation of dendritic cells (DC). Transcriptome analyses identified two distinct groups, the IFNα/ω-DC and the IFNβ-DC. In addition, the expression level of seven chemokines and several cell surface markers characteristic of DC distinguished IFNα-DC and IFNβ-DC. These differences are unlikely to impact the efficacy of T cell functional response since IFNα2-DC and IFNβ-DC were equipotent in inducing the proliferation and the polarization of allogenic naïve CD4 T cells into Th1 cells and in stimulating autologous antigen specific CD4 or CD8 T cells. Of the functional parameters analysed, the only one that showed a modest differential was the phagocytic uptake of dead cells which was higher for IFNα2-DC.
authors.affiliation: Unité Mixte de Recherche 5235, Centre National de la Recherche Scientifique, University of Montpellier II, Montpellier, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Garcin
authors.forename: Yann
authors.initials: Y
authors.lastname: Bordat
authors.forename: Paul
authors.initials: P
authors.lastname: Chuchana
authors.forename: Danièle
authors.initials: D
authors.lastname: Monneron
authors.forename: Helen K W
authors.initials: HK
authors.lastname: Law
authors.forename: Jacob
authors.initials: J
authors.lastname: Piehler
authors.forename: Gilles
authors.initials: G
authors.lastname: Uzé
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology; D059467:Transcriptome
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D012313:RNA