TY - JOUR
T1 - Tyk2 plays a restricted role in IFNα signaling, although it is required for IL-12-mediated T cell function
AU - Shimoda, Kazuya
AU - Kato, Kouji
AU - Aoki, Kenichi
AU - Matsuda, Tadashi
AU - Miyamoto, Akitomo
AU - Shibamori, Masafumi
AU - Yamashita, Masakatsu
AU - Numata, Akihiko
AU - Takase, Ken
AU - Kobayashi, Shinji
AU - Shibata, Shouichirou
AU - Asano, Yoshinobu
AU - Gondo, Hisashi
AU - Sekiguchi, Kazuo
AU - Nakayama, Keiko
AU - Nakayama, Toshinori
AU - Okamura, Takashi
AU - Okamura, Seiichi
AU - Niho, Yoshiyuki
AU - Nakayama, Kei ichi
N1 - Funding Information:
We thank Drs. T. Otsuka, H. Nakashima, T. Maruyama, Y. Nemoto, Y. Inoue, and Y. Fukumaki for discussion, and A. Koutate, A. Tomioka, Y. Yamada, and K. Shimoharada for their excellent technical assistance. This work was supported by Grants-in-Aid for Scientific Research (numbers 11770577 and 11307015) from the Ministry of Education, Science, Sports, and Culture in Japan.
PY - 2000
Y1 - 2000
N2 - Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNα, although a high concentration of IFNα can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNα-dependent signaling while being required in mediating IL-12-dependent biological responses.
AB - Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNα, although a high concentration of IFNα can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNα-dependent signaling while being required in mediating IL-12-dependent biological responses.
UR - http://www.scopus.com/inward/record.url?scp=0033711641&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033711641&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)00055-8
DO - 10.1016/S1074-7613(00)00055-8
M3 - Article
C2 - 11070174
AN - SCOPUS:0033711641
SN - 1074-7613
VL - 13
SP - 561
EP - 571
JO - Immunity
JF - Immunity
IS - 4
ER -
