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

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, Christoph Walker, Carol Sawyer, Klaus Okkenhaug, Peter Finan and Bart Vanhaesebroeck ()
Additional contact information
Khaled Ali: Ludwig Institute for Cancer Research
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
Klaus Okkenhaug: Ludwig Institute for Cancer Research
Peter Finan: Novartis Institutes for BioMedical Research
Bart Vanhaesebroeck: Ludwig Institute for Cancer Research

Nature, 2004, vol. 431, issue 7011, 1007-1011

Abstract: 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.

Date: 2004
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature02991 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:431:y:2004:i:7011:d:10.1038_nature02991

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02991

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().