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

Research output: Contribution to journalArticlepeer-review

473 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)875-881
Number of pages7
JournalNature Immunology
Issue number9
Publication statusPublished - 2002 Sept
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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