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

K Ali, A Bilancio, M Thomas, W Pearce, AM Gilfillan… - Nature, 2004 - nature.com
K Ali, A Bilancio, M Thomas, W Pearce, AM Gilfillan, C Tkaczyk, N Kuehn, A Gray, J Giddings…
Nature, 2004nature.com
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 (FcɛRI) engage
phosphoinositide 3-kinases (PI (3) Ks) to generate intracellular lipid second messenger
signals,,,. Here, we report that genetic or pharmacological inactivation of the p110δ isoform …
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 (FcɛRI) engage phosphoinositide 3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals,,,. 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.
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