Tyk2 plays a restricted role in IFNα signaling, although it is required for IL-12-mediated T cell function

Kazuya Shimoda, Kouji Kato, Kenichi Aoki, Tadashi Matsuda, Akitomo Miyamoto, Masafumi Shibamori, Masakatsu Yamashita, Akihiko Numata, Ken Takase, Shinji Kobayashi, Shouichirou Shibata, Yoshinobu Asano, Hisashi Gondo, Kazuo Sekiguchi, Keiko Nakayama, Toshinori Nakayama, Takashi Okamura, Seiichi Okamura, Yoshiyuki Niho, Kei ichi Nakayama

Research output: Contribution to journalArticlepeer-review

248 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)561-571
Number of pages11
JournalImmunity
Volume13
Issue number4
DOIs
Publication statusPublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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