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

doi:10.1038/ni825

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 journal › Article › peer-review

193 Citations (Scopus)

Abstract

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 (T_H1) 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 T_H1 polarization that causes undesirable immune responses.

Original language	English
Pages (from-to)	875-881
Number of pages	7
Journal	Nature Immunology
Volume	3
Issue number	9
DOIs	https://doi.org/10.1038/ni825
Publication status	Published - 2002 Sept
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "P13K-mediated negative feedback regulation of IL-12 production in DCs",

abstract = "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.",

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

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AU - Fukao, Taro

AU - Tanabe, Masanobu

AU - Terauchi, Yasuo

AU - Ota, Takayuki

AU - Matsuda, Satoshi

AU - Asano, Tomoichiro

AU - Kadowaki, Takashi

AU - Takeuchi, Tsutomo

AU - Koyasu, Shigeo

PY - 2002/9

Y1 - 2002/9

N2 - 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.

AB - 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.

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

Abstract

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