Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice

Kazuya Shimoda, Hiroko Tsutsui, Kenichi Aoki, Kouji Kato, Tadashi Matsuda, Akihiko Numata, Ken Takase, Tetsuya Yamamoto, Hideyuki Nukina, Tomoaki Hoshino, Yoshinobu Asano, Hisashi Gondo, Takashi Okamura, Seiichi Okamura, Kei Ichi Nakayama, Kenji Nakanishi, Yoshiyuki Niho, Mine Harada

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Tyk2 is activated in response to interleukin-12 (IL-12) and is essential for IL-12-induced T-cell function, including interferon-γ (IFN-γ) production and Th1 cell differentiation. Because IL-12 is a stimulatory factor for natural killer (NK) cell-mediated cytotoxicity, we examined whether tyk2 is required for IL-12-induced NK cell activity. IL-12-induced NK cell activity in cells from tyk2-deficient mice was drastically reduced compared to that in cells from wild-type mice. IL-18 shares its biologic functions with IL-12. However, the molecular mechanism of IL-18 signaling, which activates an IL-1 receptor-associated kinase and nuclear translocation of nuclear factor-KB, is different from that of IL-12. We next examined whether biologic functions induced by IL-18 are affected by the absence of tyk2. NK cell activity and IFN-γ production induced by IL-18 were reduced by the absence of tyk2. Moreover, the synergistic effect of IL-12 and IL-18 for the production of IFN-γ was also abrogated by the absence of tyk2. This was partially due to the absence of any up-regulation of the IL-18 receptor treated with IL-12, and it might suggest the presence of the crosstalk between Jak-Stat and mitogen-activated protein kinase pathways in cytokine signaling.

Original languageEnglish
Pages (from-to)2094-2099
Number of pages6
JournalBlood
Volume99
Issue number6
DOIs
Publication statusPublished - Mar 15 2002

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Interleukin-18
Interleukin-12
Natural Killer Cells
Interferons
Interleukin-18 Receptors
Interleukin-1 Receptor-Associated Kinases
Th1 Cells
T-cells
Cytotoxicity
Crosstalk
Mitogen-Activated Protein Kinases
Cell Differentiation
Up-Regulation
Cytokines
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice. / Shimoda, Kazuya; Tsutsui, Hiroko; Aoki, Kenichi; Kato, Kouji; Matsuda, Tadashi; Numata, Akihiko; Takase, Ken; Yamamoto, Tetsuya; Nukina, Hideyuki; Hoshino, Tomoaki; Asano, Yoshinobu; Gondo, Hisashi; Okamura, Takashi; Okamura, Seiichi; Nakayama, Kei Ichi; Nakanishi, Kenji; Niho, Yoshiyuki; Harada, Mine.

In: Blood, Vol. 99, No. 6, 15.03.2002, p. 2094-2099.

Research output: Contribution to journalArticle

Shimoda, K, Tsutsui, H, Aoki, K, Kato, K, Matsuda, T, Numata, A, Takase, K, Yamamoto, T, Nukina, H, Hoshino, T, Asano, Y, Gondo, H, Okamura, T, Okamura, S, Nakayama, KI, Nakanishi, K, Niho, Y & Harada, M 2002, 'Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice', Blood, vol. 99, no. 6, pp. 2094-2099. https://doi.org/10.1182/blood.V99.6.2094
Shimoda, Kazuya ; Tsutsui, Hiroko ; Aoki, Kenichi ; Kato, Kouji ; Matsuda, Tadashi ; Numata, Akihiko ; Takase, Ken ; Yamamoto, Tetsuya ; Nukina, Hideyuki ; Hoshino, Tomoaki ; Asano, Yoshinobu ; Gondo, Hisashi ; Okamura, Takashi ; Okamura, Seiichi ; Nakayama, Kei Ichi ; Nakanishi, Kenji ; Niho, Yoshiyuki ; Harada, Mine. / Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice. In: Blood. 2002 ; Vol. 99, No. 6. pp. 2094-2099.
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AU - Matsuda, Tadashi

AU - Numata, Akihiko

AU - Takase, Ken

AU - Yamamoto, Tetsuya

AU - Nukina, Hideyuki

AU - Hoshino, Tomoaki

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AU - Gondo, Hisashi

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