Multiple sclerosis: interferon-beta induces CD123+BDCA2− dendritic cells that produce IL-6 and IL-10 and have no enhanced type I interferon production

Interferon-beta (IFN-β), an approved drug for multiple sclerosis (MS), acts on dendritic cells (DC) by suppressing IL-12p40 and increasing IL-10. This results in Th2-biased immune responses. The nature of IFN-β-modulated DC remains elusive. Previously, we observed that IFN-β  dose dependently induces expression of CD123, i.e., a classical marker for plasmacytoid DC, on human blood monocyte-derived myeloid DC. Such IFN-β-modulated DCs produce predominantly IL-10 but are IL-12 deficient, with potent Th2 promotion. In the present study, we further characterize IFN-β-modulated DC by using recently identified blood DC antigens (BDCA), and investigate their ability to produce type I IFN in response to virus stimulation. We show that IFN-β induces development of CD123+ DC from human blood monocytes, which coexpress BDCA4+ but are negative for BDCA2−, a specific marker for plasmacytoid DC. Such IFN-β-modulated DC can produce IL-6 and IL-10 but not IL-12p40, and have no enhanced IFN-α and IFN-β production. The findings indicate that IFN-β-modulated DCs represent a myeloid DC subset with diminished CD11c, BDCA-1 and CD1a expression. They may promote Th2 and B cell differentiation through IL-6 and IL-10 production, and suppression of IL-12p40, but they have no enhanced antiviral capacity.