title: Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice.
abstract: Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells. Accordingly, these mice show impaired bacterial clearance in response to acute septic peritonitis and are highly susceptible to infection by the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock responses, however, are intact. We found that although reconstitution of PI3Kminus sign/minus sign mice with bone marrow--derived mast cells (BMMCs) restored anti-bacterial immunity, only T helper type 2 (TH2)-conditioned BMMCs, not "standard" BMMCs, were able to restore anti-nematode immunity. This finding highlights the importance of the TH2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells.
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: Taketo
authors.initials: T
authors.lastname: Yamada
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: Tetsuro
authors.initials: T
authors.lastname: Takayama
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hata Ji
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004064:Digestive System / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate; D008214:Lymphocytes / Q000276:immunology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013322:Strongyloidiasis / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit