Parlato Stefania, Bruni Roberto, Fragapane Paola, Salerno Debora, Marcantonio Cinzia, Borghi Paola, Tataseo Paola, Ciccaglione Anna Rita, Presutti Carlo, Romagnoli Giulia, Bozzoni Irene, Belardelli Filippo, Gabriele Lucia
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
PLoS One. 2013 Aug 16;8(8):e72833. doi: 10.1371/journal.pone.0072833. eCollection 2013.
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.
I型干扰素（IFN-I）已成为控制树突状细胞（DC）分化和功能的细胞信号的关键介质。在IFN-α存在下从单核细胞分化而来的人DC（IFN-α DC）表现出部分成熟的表型以及刺激CD4 + T细胞和交叉启动CD8 + T细胞的特殊能力。同样，浆细胞样DC（pDC）是血液中的DC，高度专门化以响应病毒和其他危险信号产生IFN-α，其功能特征可能由IFN-I塑造。在这里，我们研究了IFN-α刺激驱动人单核细胞来源的DC分化的分子机制，并对外周未刺激和IFN-α处理的pDC进行了平行研究。在IFN-α DC中诱导了特定的miRNA特征，并且所选的miRNA，其中miR-23a和miR-125b，被证明与IFN-α驱动的DC分化过程中发生的Blimp-1上调呈负相关。值得注意的是，单核细胞来源的IFN-α DC和体外IFN-α处理的pDC共享调节Blimp-1表达的受限miRNA模式以及一些相似的表型、分子和功能特征，支持这些DC群体之间存在潜在关系。总体而言，这些数据揭示了Blimp-1在IFN-α驱动的人DC分化中的新作用，并将Blimp-1鉴定为IFN-α介导的关键调节因子，可能解释了IFN-α DC和pDC之间共享的功能特征。
