title: PI3K and negative regulation of TLR signaling.
abstract: Excessive immune responses are detrimental to the host and negative feedback regulation is crucial for the maintenance of immune-system integrity. Recent studies have shown that phosphoinositide 3-kinase (PI3K) is an endogenous suppressor of interleukin-12 (IL-12) production triggered by Toll-like receptor (TLR) signaling and limits excessive Th1 polarization. Unlike IRAK-M (IL-1 receptor-associated kinase-M) and SOCS-1 (suppressor of cytokine signaling-1) that are induced by TLR signaling and function during the second or continuous exposure to stimulation, PI3K functions at the early phase of TLR signaling and modulates the magnitude of the primary activation. Thus, PI3K, IRAK-M and SOCS-1 have unique roles in the gate-keeping system, preventing excessive innate immune responses.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Fukao
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005246:Feedback; D006801:Humans; D007113:Immunity, Innate; D053592:Interleukin-1 Receptor-Associated Kinases; D018664:Interleukin-12 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018448:Models, Immunological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D018664:Interleukin-12; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse