title: PI3K-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 (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#150;treated DCs showed increased IL-12 production. Accordingly, an enhanced T helper type 1 (T(H)1) 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 T(H)1 polarization that causes undesirable immune responses.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Fukao
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tanabe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ota
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuda
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D005246:Feedback; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018664:Interleukin-12; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases