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- Title
Essential role for the p110delta phosphoinositide 3-kinase in the allergic response.
- Authors
Ali, Khaled; Bilancio, Antonio; Thomas, Matthew; Pearce, Wayne; Gilfillan, Alasdair M; Tkaczyk, Christine; Kuehn, Nicolas; Gray, Alexander; Giddings, June; Peskett, Emma; Fox, Roy; Bruce, Ian; Walker, Christoph; Sawyer, Carol; Okkenhaug, Klaus; Finan, Peter; Vanhaesebroeck, Bart
- Abstract
Inflammatory substances released by mast cells induce and maintain the allergic response. 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). Activated SCF receptors and high-affinity receptors for IgE (FcvarepsilonRI) engage phosphoinositide 3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals. Here, we report that genetic or pharmacological inactivation of the p110delta 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 p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies.
- Publication
Nature, 2004, Vol 431, Issue 7011, p1007
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature02991