Heystek H C, den Drijver B, Kapsenberg M L, van Lier R A W, de Jong E C
Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
Clin Immunol. 2003 Jun;107(3):170-7. doi: 10.1016/s1521-6616(03)00060-3.
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.
I型干扰素（IFNα/β）已被批准用于治疗多种疾病，包括自身免疫性疾病多发性硬化症（MS）。促炎细胞因子IL-12和IFN-γ被认为与MS的发病机制有关。由于树突状细胞（DCs）被认为是IL-12p70的主要产生者，并促进产生IFN-γ的Th1细胞的发育，我们研究了IFNα/β在不同发育阶段对单核细胞来源的DCs的直接作用。我们证明，IFNα/β增强未成熟DCs产生IL-12p70的能力，但抑制成熟DCs产生IL-12p70的能力。重要的是，无论DCs的成熟状态如何，IFNα/β都能强烈抵消IFN-γ对DCs的IL-12增强作用。在成熟过程中，DCs暴露于IFNα/β不会影响其在CD40连接后的成熟或细胞因子谱。IFNα/β对DCs产生IL-12能力的不同调节作用及其对IFN-γ的交叉调节作用可能会减少炎症过程，因此在MS治疗中可能有效。
