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-beta), 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-beta-modulated DC remains elusive. Previously, we observed that IFN-beta dose dependently induces expression of CD123, i.e., a classical marker for plasmacytoid DC, on human blood monocyte-derived myeloid DC. Such IFN-beta-modulated DCs produce predominantly IL-10 but are IL-12 deficient, with potent Th2 promotion. In the present study, we further characterize IFN-beta-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-beta 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-beta-modulated DC can produce IL-6 and IL-10 but not IL-12p40, and have no enhanced IFN-alpha and IFN-beta production. The findings indicate that IFN-beta-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.
Huang
Y M
YM
Division of Neuroimmunology, Karolinska Institute, Alfred Nobels allé 10, 141 83 Stockholm, Sweden. yu-min.huang@neurotec.ki.se
Adikari
S
S
Båve
U
U
Sanna
A
A
Alm
G
G
D000328:Adult; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004185:Disability Evaluation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism*; D053650:Interleukin-3 Receptor alpha Subunit; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D029082:Sendai virus / Q000472:pathogenicity / Q000502:physiology; D018139:Simplexvirus / Q000472:pathogenicity / Q000502:physiology
C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D015850:Interleukin-6; D016185:Receptors, Interleukin-3; D016753:Interleukin-10; D016899:Interferon-beta