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Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice

Nature Immunology volume 3, pages 295–304 (2002)Cite this article

Abstract

Mice that lack the p85α 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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Figure 1: Impaired acute bacterial clearance in PI3K−/− mice.
Figure 2: Selective loss of gastrointestinal mast cells in PI3K−/− mice.
Figure 3: IgE-dependent passive systemic anaphylaxis in PI3K−/− mice.
Figure 4: Gastrointestinal mast cells were restored in PI3K−/− mice by bone marrow transplantation.
Figure 5: Defective SCF-induced proliferation in PI3K−/− BMMCs.
Figure 6: Modest mastocytosis and delayed expulsion of adult worms in PI3K−/− mice infected with S. venezuelensis.
Figure 7: Restoration of anti-parasitic immunity in PI3K−/− mice by reconstitution with TH2-conditioned BMMCs.

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Acknowledgements

We thank M. Motouchi and K. Furuichi for animal care; S. Matsuda for valuable discussions; L. K. Clayton and J. Fujimoto for critical reading of the manuscript; and the Department of Dermatology of Keio University School of Medicine for experimental equipment. Supported by a Keio University Special Grant-in-Aid for Innovative Collaborative Research Project; a grant for the Research For The Future Program (JSPS-RFTF-97L00701) from the Japan Society for the Promotion of Science; a Grant-in-Aid for Scientific Research on Priority Areas (C) (13226112); a National Grant-in-Aid for the Establishment of a High-Tech Research Center in a Private University; a grant for the Promotion of the Advancement of Education and Research in Graduate Schools; and a Scientific Frontier Research Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Taro Fukao, Takayuki Ota, Tetsuro Takayama & Shigeo Koyasu

  2. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Taketo Yamada & Jun-ichi Hata

  3. Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Masanobu Tanabe & Tsutomu Takeuchi

  4. Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan

    Yasuo Terauchi, Tomoichiro Asano & Takashi Kadowaki

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Fukao, T., Yamada, T., Tanabe, M. et al. Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nat Immunol 3, 295–304 (2002). https://doi.org/10.1038/ni768

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