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.
Highlights
IFN-I are pleiotropic cytokines that coordinate innate and adaptive immune responses
(pDC) and conventional DC associated with natural killer (NK) cell characteristics [6]. 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 exposure to IFN-I
We report that IFN-α controls B lymphocyte-induced maturation protein-1 (Blimp-1) expression during human DC differentiation associated with down-regulation of a selected pattern of miRNAs among which miR-23a and miR-125b are the major players
Summary
IFN-I are pleiotropic cytokines that coordinate innate and adaptive immune responses. Our group as well as other laboratories reported that human DC differentiated from peripheral monocytes in the presence of IFN-α (IFN-α DC) represent highly activated DC capable of efficiently inducing CD8+ T cells against both viral and tumor antigens [2,3,4]. IFN-α DC have been shown to retain phagocytic activity, in spite of their partial mature phenotype, and to own a special capability of stimulating CD4+ T helper lymphocytes and inducing crosspriming of CD8+ T cells [5]. 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 exposure to IFN-I. The mechanisms underlying the ability of IFN-α to confer DC with unique functions as well as those regulating IFN-I influence on pDC development and function remain unclear
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