Defining features of chronic airway diseases include abnormal and persistent inflammatory processes, impaired airway epithelial integrity and function, and increased susceptibility to recurrent respiratory infections. Phosphoinositide 3-kinases (PI3K) are lipid kinases, which contribute to multiple physiological and pathological processes within the airway, with abnormal PI3K signalling contributing to the pathogenesis of several respiratory diseases. Consequently, the potential benefit of targeting PI3K isoforms has received considerable attention, being viewed as a viable therapeutic option in inflammatory and infectious lung disorders. The class I PI3K isoform, PI3Kδ (Phosphoinositide 3-kinases δ) is of particular interest given its multiple roles in modulating innate and adaptive immune cell functions, airway inflammation and corticosteroid sensitivity. In this mini-review, we explore the role of PI3Kδ in airway inflammation and infection, focusing on oxidative stress, ER stress, histone deacetylase 2 and neutrophil function. We also describe the importance of PI3Kδ in adaptive immune cell function, as highlighted by the recently described Activated PI3K Delta Syndrome, and draw attention to some of the potential clinical applications and benefits of targeting this molecule.
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April 2018
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A 3D rendering of a Ubiquitin protein molecule. In this issue of Biochemical Society Transactions, Ovaa and Vertegaal discuss the role of ubiquitination and SUMO proteins in conjugation and deconjugation machineries; for details, see pages 423–436.
Review Article|
March 09 2018
Phosphoinositide 3-kinase δ (PI3Kδ) in respiratory disease
Clare A. Stokes;
Clare A. Stokes
1Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, U.K.
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Alison M. Condliffe
1Department of Infection, Immunity and Cardiovascular Disease, School of Medicine, Dentistry and Health, University of Sheffield, Sheffield, U.K.
Correspondence: Alison M. Condliffe (a.m.condliffe@sheffield.ac.uk)
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Publisher: Portland Press Ltd
Received:
December 20 2017
Revision Received:
January 29 2018
Accepted:
February 05 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (2): 361–369.
Article history
Received:
December 20 2017
Revision Received:
January 29 2018
Accepted:
February 05 2018
Citation
Clare A. Stokes, Alison M. Condliffe; Phosphoinositide 3-kinase δ (PI3Kδ) in respiratory disease. Biochem Soc Trans 17 April 2018; 46 (2): 361–369. doi: https://doi.org/10.1042/BST20170467
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