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Essential role for the p110δ phosphoinositide 3-kinase in the allergic response

Author

Listed:
  • Khaled Ali

    (Ludwig Institute for Cancer Research
    University College London)

  • Antonio Bilancio

    (Ludwig Institute for Cancer Research)

  • Matthew Thomas

    (Novartis Institutes for BioMedical Research)

  • Wayne Pearce

    (Ludwig Institute for Cancer Research)

  • Alasdair M. Gilfillan

    (National Institutes of Health)

  • Christine Tkaczyk

    (National Institutes of Health)

  • Nicolas Kuehn

    (Frimorfo)

  • Alexander Gray

    (University of Dundee)

  • June Giddings

    (Novartis Institutes for BioMedical Research)

  • Emma Peskett

    (Ludwig Institute for Cancer Research)

  • Roy Fox

    (Novartis Institutes for BioMedical Research)

  • Ian Bruce

    (Novartis Institutes for BioMedical Research)

  • Christoph Walker

    (Novartis Institutes for BioMedical Research)

  • Carol Sawyer

    (Ludwig Institute for Cancer Research
    Institute of Cancer Research)

  • Klaus Okkenhaug

    (Ludwig Institute for Cancer Research
    the Babraham Institute)

  • Peter Finan

    (Novartis Institutes for BioMedical Research)

  • Bart Vanhaesebroeck

    (Ludwig Institute for Cancer Research
    University College London)

Abstract

Inflammatory substances released by mast cells induce and maintain the allergic response1,2. Mast cell differentiation and activation are regulated, respectively, by stem cell factor (SCF; also known as Kit ligand) and by allergen in complex with allergen-specific immunoglobulin E (IgE)2,3. Activated SCF receptors and high-affinity receptors for IgE (FcɛRI) engage phosphoinositide 3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals2,3,4,5. Here, we report that genetic or pharmacological inactivation of the p110δ isoform of PI(3)K in mast cells leads to defective SCF-mediated in vitro proliferation, adhesion and migration, and to impaired allergen–IgE-induced degranulation and cytokine release. Inactivation of p110δ protects mice against anaphylactic allergic responses. These results identify p110δ as a new target for therapeutic intervention in allergy and mast-cell-related pathologies.

Suggested Citation

  • Khaled Ali & Antonio Bilancio & Matthew Thomas & Wayne Pearce & Alasdair M. Gilfillan & Christine Tkaczyk & Nicolas Kuehn & Alexander Gray & June Giddings & Emma Peskett & Roy Fox & Ian Bruce & Christ, 2004. "Essential role for the p110δ phosphoinositide 3-kinase in the allergic response," Nature, Nature, vol. 431(7011), pages 1007-1011, October.
    • Handle: RePEc:nat:nature:v:431:y:2004:i:7011:d:10.1038_nature02991
    DOI: 10.1038/nature02991
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