IFN-α Regulates Blimp-1 Expression via miR-23a and miR-125b in Both Monocytes-Derived DC and pDC

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-alpha (IFN-alpha 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-alpha 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-alpha in driving human monocyte-derived DC differentiation and performed parallel studies on peripheral unstimulated and IFN-alpha-treated pDC. A specific miRNA signature was induced in IFN-alpha 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-alpha-driven DC differentiation. Of note, monocyte-derived IFN-alpha DC and in vitro IFN-alpha-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-alpha and identify Blimp-1 as an IFN-alpha-mediated key regulator potentially accounting for shared functional features between IFN-alpha DC and pDC.