P13K-mediated negative feedback regulation of IL-12 production in DCs

Taro Fukao, Masanobu Tanabe, Yasuo Terauchi, Takayuki Ota, Satoshi Matsuda, Tomoichiro Asano, Takashi Kadowaki, Tsutomo Takeuchi, Shigeo Koyasu

研究成果: Article査読

444 被引用数 (Scopus)

抄録

Although interleukin 12 (IL-12) production by dendritic cells (DCs) confers protection against harmful invasions by regulating both innate and adaptive immunity, its dysregulation may have detrimental effects on the host. We show here that phosphoinositide 3-kinase (P13K) negatively regulates IL-12 synthesis by DCs. We found that numerous stimuli that induced IL-12 production concomitantly elicited P13K activation in DCs, but both P13K−/− and P13K inhibitor-treated DCs showed increased IL-12 production. Accordingly, an enhanced T helper type I (TH1) response was observed upon Leishmania major infection in P13K−/− mice. Our findings indicate that a negative feedback mechanism exists that regulates IL-12 production during DC activation and may help prevent the excessive TH1 polarization that causes undesirable immune responses.

本文言語English
ページ(範囲)875-881
ページ数7
ジャーナルNature Immunology
3
9
DOI
出版ステータスPublished - 2002 9
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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