title: IFN-α regulates Blimp-1 expression via miR-23a and miR-125b in both monocytes-derived DC and pDC.
abstract: Type I interferon (IFN-I) have emerged as crucial mediators of cellular signals controlling DC differentiation and function. Human DC differentiated from monocytes in the presence of IFN-α (IFN-α DC) show a partially mature phenotype and a special capability of stimulating CD4+ T cell and cross-priming CD8+ T cells. Likewise, plasmacytoid DC (pDC) are blood DC highly specialized in the production of IFN-α in response to viruses and other danger signals, whose functional features may be shaped by IFN-I. Here, we investigated the molecular mechanisms stimulated by IFN-α in driving human monocyte-derived DC differentiation and performed parallel studies on peripheral unstimulated and IFN-α-treated pDC. A specific miRNA signature was induced in IFN-α DC and selected miRNAs, among which miR-23a and miR-125b, proved to be negatively associated with up-modulation of Blimp-1 occurring during IFN-α-driven DC differentiation. Of note, monocyte-derived IFN-α DC and in vitro IFN-α-treated pDC shared a restricted pattern of miRNAs regulating Blimp-1 expression as well as some similar phenotypic, molecular and functional hallmarks, supporting the existence of a potential relationship between these DC populations. On the whole, these data uncover a new role of Blimp-1 in human DC differentiation driven by IFN-α and identify Blimp-1 as an IFN-α-mediated key regulator potentially accounting for shared functional features between IFN-α DC and pDC.
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Stefania
authors: S
authors: Parlato
authors: Roberto
authors: R
authors: Bruni
authors: Paola
authors: P
authors: Fragapane
authors: Debora
authors: D
authors: Salerno
authors: Cinzia
authors: C
authors: Marcantonio
authors: Paola
authors: P
authors: Borghi
authors: Paola
authors: P
authors: Tataseo
authors: Anna Rita
authors: AR
authors: Ciccaglione
authors: Carlo
authors: C
authors: Presutti
authors: Giulia
authors: G
authors: Romagnoli
authors: Irene
authors: I
authors: Bozzoni
authors: Filippo
authors: F
authors: Belardelli
authors: Lucia
authors: L
authors: Gabriele
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000166:cytology*; D010641:Phenotype; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; C531888:MIRN125 microRNA, human; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1
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