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The Role of TNFα and IL-17 in the Development of Excess IL-1 Signaling-Induced Inflammatory Diseases in IL-1 Receptor Antagonist-Deficient Mice

  • Conference paper
Cytokines as Potential Therapeutic Targets for Inflammatory Skin Diseases

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 56))

Abstract

IL-1 receptor antagonist (IL-1Ra)-deficient mice spontaneously develop several inflammatory diseases, resembling rheumatoid arthritis, aortitis, and psoriasis in humans. As adoptive T cell transplantation could induce arthritis and aortitis in recipient mice, it was suggested that an autoimmune process is involved in the development of diseases. In contrast, as dermatitis developed in scid/scid-IL-1Ra-deficient mice and could not be induced by T cell transfer, a T cell-independent mechanism was suggested. The expression of proinflammatory cytokines was augmented at the inflammatory sites. The development of arthritis and aortitis was significantly suppressed by the deficiency of TNFα or IL-17. The development of dermatitis was also inhibited by the deficiency of TNFα. These observations suggest that TNFα and IL-17 play a crucial role in the development of autoimmunity downstream of IL-1 signaling, and excess IL-1 signaling-induced TNFα also induces skin inflammation in a T cell-independent manner.

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Authors and Affiliations

  1. Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    H. Ishigame, A. Nakajima, S. Saijo, Y. Komiyama, T. Matsuki, S. Nakae, R. Horai, S. Kakuta & Y. Iwakura

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  1. H. Ishigame
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  2. A. Nakajima
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  3. S. Saijo
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  4. Y. Komiyama
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  5. A. Nambu
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  6. T. Matsuki
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  7. S. Nakae
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  8. R. Horai
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Editors and Affiliations

  1. Berlex Biosciences, 2600 Hilltop Drive, PO Box 4099, Richmond, CA, 94804-0099, USA

    R. Numerof

  2. University of Colorado Health Sciences Center, 4200 East Ninth Ave., B168, Denver, CO, 80262, USA

    C. A. Dinarello

  3. Corporate Research Business Area Dermatology, Schering AG, Müllerstr. 178, 13342, Berlin, Germany

    K. Asadullah

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Ishigame, H. et al. (2005). The Role of TNFα and IL-17 in the Development of Excess IL-1 Signaling-Induced Inflammatory Diseases in IL-1 Receptor Antagonist-Deficient Mice. In: Numerof, R., Dinarello, C.A., Asadullah, K. (eds) Cytokines as Potential Therapeutic Targets for Inflammatory Skin Diseases. Ernst Schering Research Foundation Workshop, vol 56. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-37673-9_8

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