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IL-18

Regulation and Physiological Roles of IL-18

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Abstract

Interleukin-18 (IL-18) belongs to the IL-1 cytokine family, which has crucial roles in innate immunity and inflammation. These cytokines share similar molecular structures, receptor structures, and signal transduction pathways. Each cytokine, however, acts on distinct types of cells that express their specific receptor. The functional IL-18 receptor is specifically induced by cytokines such as IL-2 and IL-12. During innate immune responses, IL-1β acts primarily on Th17 cells, leading to the recruitment of neutrophils, whereas IL-18 in the presence of IL-2 or IL-12 induces Th1-type responses in natural killer (NK) and CD8+ T cells, which induces reactive oxygen species and nitric oxide production in macrophages. IL-18 is constitutively expressed in hematopoietic cells and nonhematopoietic cells in tissues where cells are rapidly dividing. Similar to IL-1β, the inactive precursor of IL-18 is proteolytically converted to a mature form by caspase-1 in inflammasome complexes. Although the molecular mechanism by which IL-18 is activated by inflammasomes has been clarified, the regulatory mechanism underlying the expression of IL-18 receptors, the effect of signaling on organelles such as mitochondria, and the biological roles of IL-18 in nonhematopoietic cells remain to be elucidated. Accumulating evidence suggests that IL-18 is not merely a cytokine inducer, but a molecule involved in the viability and terminal differentiation of various cells.

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Wen Li & Haruki Okamura

  2. Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yoshimasa Tanaka

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  1. Wen Li
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  2. Yoshimasa Tanaka
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  3. Haruki Okamura
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Correspondence to Haruki Okamura .

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Editors and Affiliations

  1. Department of Immunoregulation Institute of Medical Science, Tokyo Medical University, Tokyo, Tokyo, Japan

    Takayuki Yoshimoto

  2. Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Tomohiro Yoshimoto

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Li, W., Tanaka, Y., Okamura, H. (2014). IL-18. In: Yoshimoto, T., Yoshimoto, T. (eds) Cytokine Frontiers. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54442-5_4

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