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 language | English |
|---|---|
| Pages (from-to) | 2094-2099 |
| Number of pages | 6 |
| Journal | Blood |
| Volume | 99 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice
AU - Shimoda, Kazuya
AU - Tsutsui, Hiroko
AU - Aoki, Kenichi
AU - Kato, Kouji
AU - Matsuda, Tadashi
AU - Numata, Akihiko
AU - Takase, Ken
AU - Yamamoto, Tetsuya
AU - Nukina, Hideyuki
AU - Hoshino, Tomoaki
AU - Asano, Yoshinobu
AU - Gondo, Hisashi
AU - Okamura, Takashi
AU - Okamura, Seiichi
AU - Nakayama, Kei Ichi
AU - Nakanishi, Kenji
AU - Niho, Yoshiyuki
AU - Harada, Mine
PY - 2002/3/15
Y1 - 2002/3/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0037085783&partnerID=8YFLogxK
U2 - 10.1182/blood.V99.6.2094
DO - 10.1182/blood.V99.6.2094
M3 - Article
C2 - 11877284
AN - SCOPUS:0037085783
VL - 99
SP - 2094
EP - 2099
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -