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The Journal of Immunology, 2000, 164: 64-71.
Copyright © 2000 by The American Association of Immunologists

Synergistic Effects of IL-4 and IL-18 on IL-12-Dependent IFN-{gamma} Production by Dendritic Cells1

Taro Fukao, Satoshi Matsuda and Shigeo Koyasu2

Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan

Mouse splenic dendritic cells (DCs) produce IFN-{gamma} in response to IL-12. In the present study, we analyzed effects of Th1 and Th2 cytokines on IFN-{gamma} production by DCs. IL-18 produced by DCs and macrophages acts in an autocrine manner and augments IL-12-induced IFN-{gamma} production by DCs as also observed in T and NK cells. Surprisingly, IL-4, a Th2 cytokine, also acts synergistically with IL-12 on IFN-{gamma} production by DCs. In addition, IL-4 markedly enhances IFN-{gamma} production when DCs are stimulated through CD40 or MHC class II. These results indicate that both Th1 and Th2 cytokines act on DCs during T cell-DC interaction upon Ag presentation. p38 mitogen-activated protein kinase is constitutively activated in mature DCs and is required for IFN-{gamma} production by DCs. IL-18 but not IL-4 or IL-12 further activates the p38 mitogen-activated protein kinase activity, suggesting that IL-4 and IL-18 enhance IFN-{gamma} production through distinct intracellular signal transduction pathways in DCs.




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