Nature Immunology
3, 295 - 304 (2002)
Published online: 19 February 2002; | doi:10.1038/ni768
Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient miceTaro Fukao1, Taketo Yamada2, Masanobu Tanabe3, Yasuo Terauchi4, Takayuki Ota1, Tetsuro Takayama1, Tomoichiro Asano4, Tsutomu Takeuchi3, Takashi Kadowaki4, Jun-ichi Hata2
& Shigeo Koyasu11
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. 2
Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. 3
Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. 4
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Correspondence should be addressed to Shigeo Koyasu koyasu@sc.itc.keio.ac.jpMice that lack the p85 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 PI3K-/- 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.
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