Multiple Sclerosis: IFN‐β Induces CD123(+)BDCA2(–) Dendritic Cells that Produce IL‐6 and IL‐10 and have No Enhanced Type I Interferon Production

Huang, Y. M.; Adikari, S.; BÃ¥ve, U.; Sanna, A.; Alm, G.

IFN‐β, an approved drug for multiple sclerosis (MS), acts on dendritic cell (DC) by suppressing their production of 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 DC 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 produce large amounts of IL‐6 and IL‐10, but no IL‐12p40 and have no enhanced IFN‐β and IFN‐β production. The findings indicate that IFN‐β‐modulated DC represent a myeloid DC subset with diminished CD11c, BDCA‐1 and CD1a expression, having potent Th2‐promoting function but lacking antiviral capacity.