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IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6

Nature Immunology volume 1, pages 132–137 (2000)Cite this article

Abstract

Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (T H2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1–like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells−, IL-4– and STAT6–dependent fashion. IL-18 and T cell receptor–mediated stimulation could induce naïve CD4+ T cells to develop into IL-4–producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.

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Figure 1: IL-18–induced IgE, IL-4 and IL-13 production in vivo is dependent on CD4+ T cells.
Figure 2: IL-18–induced IgE production in vivo is dependent on IL-4.
Figure 3: IL-18 secreted in caspase-1 Tg mice induced IgE production in vivo by activation of STAT6.
Figure 4: IL-18 stimulated CD4+ T cells to up-regulate CD40L expression and to cause B cells to produce IgE in vitro.
Figure 5: IL-18 stimulates naïve CD4+ T cells to develop into TH2 cells in the presence of TCR engagement in vitro.
Figure 6: IL-18 expression in patients suffering from leprosy.

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Acknowledgements

We thank Hayashibara Biochemical Laboratories Inc. for providing recombinant murine IL-18, S. Akira and K. Takeda at Osaka University for STAT6−/− and IL-18−/− mice, M. Kobayashi and the Research Support Team at Genetic Institute for murine sIL-13Pα—Fc and H. Fukui for excellent technical assistance. Supported by Grant-in-Aid for Scientific Research and Hitech Research Center grant from the Ministry of Education, Science and Culture of Japan.

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Authors and Affiliations

  1. Department of Immunology and Medical Zoology, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya , 663-8501, Hyogo, Japan

    Tomohiro Yoshimoto, Hiroko Tsutsui & Kenji Nakanishi

  2. Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, 663-8501, Hyogo, Japan

    Tomohiro Yoshimoto, Haruki Okamura & Kenji Nakanishi

  3. Department of Dermatology, Mie University, Faculty of Medicine, Tsu, 514-8507, Mie, Japan

    Hitoshi Mizutani & Kei-ichi Yamanaka

  4. Department of Biochemistry, Mie University, Faculty of Medicine, Tsu, 514-8507, Mie, Japan

    Minoru Tanaka

  5. National Leprosarium, Oshima Seisho-En , Kagawa, 761-0198, Japan

    Shinzo Izumi

  6. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda , 20892-1892, MD, USA

    Nancy Noben-Trauth & William E. Paul

  7. Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan

    Tomohiro Yoshimoto & Kenji Nakanishi

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  1. Tomohiro Yoshimoto
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Correspondence to Kenji Nakanishi.

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Yoshimoto, T., Mizutani, H., Tsutsui, H. et al. IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6. Nat Immunol 1, 132–137 (2000). https://doi.org/10.1038/77811

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