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IL-18 and IL-18 Receptor Knockout Mice

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Cytokine Knockouts

Part of the book series: Contemporary Immunology ((CONTIM))

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Abstract

Interferon-γ (IFN-γ), a primary cytokine for the development of inflammatory responses, plays an essential role in host defense but has the potential to induce pathologic changes. Initially, IFN-γ was believed to be produced by limited sets of cells, such as T-cells and natural killer (NK) cells. T-cells need to develop into T-helper type 1 (Thl) cells to gain the capacity to produce IFN-γ in response to antigen (Ag) (1). In contrast, NK cells can produce IFN-γ in response to IL-12 without such differentiation (2). Discovery of IL-18 significantly changed this scenario for explaining IFN-γ production (3–10). First, upon stimulation with IL-18 and IL-12 without T-cell receptor (TCR) engagement, freshly isolated Th cells and Thl cells can produce higher levels of IFN-γ than Ag-stimulated Thl cells. IL-18 only moderately upregulates IFN-γ production by Thl cells stimulated with TCR engagement. Moreover, IL-18, unlike IL-12, has no activity to induce Thl cell development in naive Th cells per se (11). These findings suggest a minor role for IL-18 in adaptive immunity, but the importance of IL-18 in innate immunity. Second, IL-18 synergizes with IL-12 for IFN-γ production by a wide range of cell types, including NK cells, and B-cells, macrophages, dendritic cells, and smooth muscle cells (9,12–15). This TCR engagement-independent IFN-γ induction is a unique property of IL-18/IL-12 biology (Fig. 1).

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  1. Hiroko Tsutsui
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    Giamila Fantuzzi PhD

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Tsutsui, H., Yoshimoto, T., Okamura, H., Akira, S., Nakanishi, K. (2003). IL-18 and IL-18 Receptor Knockout Mice. In: Fantuzzi, G. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-405-4_18

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