Nature Immunology
3, 875 - 881 (2002)
Published online: 5 August 2002; | doi:10.1038/ni825
PI3K-mediated negative feedback regulation of IL-12 production in DCsTaro Fukao1, Masanobu Tanabe2, Yasuo Terauchi3, Takayuki Ota1, 4, Satoshi Matsuda1, Tomoichiro Asano3, Takashi Kadowaki3, Tsutomu Takeuchi2
& Shigeo Koyasu11
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. 2
Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. 3
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. 4
Present address: Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Correspondence should be addressed to Shigeo Koyasu koyasu@sc.itc.keio.ac.jpAlthough 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 (PI3K) negatively regulates IL-12 synthesis by DCs. We found that numerous stimuli that induced IL-12 production concomitantly elicited PI3K activation in DCs, but both PI3K-/- and PI3K inhibitor−treated DCs showed increased IL-12 production. Accordingly, an enhanced T helper type 1 (TH1) response was observed upon Leishmania major infection in PI3K-/- 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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