Clin Immunol. 2003 Jun;107(3):170-7
Heystek HC, den Drijver B, Kapsenberg ML, van Lier RA, de Jong EC.
Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
Type I IFNs (IFNalpha/beta) are approved for the treatment of a variety of diseases, including the autoimmune disease multiple sclerosis (MS).
The proinflammatory cytokines IL-12 and IFN-gamma have been proposed to contribute to the pathogenesis of MS.
Since dendritic cells (DCs) are recognized as major producers of IL-12p70 and promote the development of IFN-gamma-producing Th1 cells, we investigated the direct effect of IFNalpha/beta on monocyte-derived DCs at different stages of development.
We demonstrate that IFNalpha/beta enhance IL-12p70 production by immature DCs but inhibit IL-12p70 production by mature DCs.
Importantly, IFNalpha/beta strongly counteracted the IL-12-enhancing effect of IFN-gamma on DCs irrespective of their maturation status.
Exposure of DCs to IFNalpha/beta during maturation does not affect their maturation or cytokine profile upon CD40 ligation.
The differential modulatory effect of IFNalpha/beta on the IL-12-producing capacity of DCs and their cross-regulatory effect on IFN-gamma may reduce inflammatory processes and therefore be therapeutically effective in MS.