Lucas, C.L., Chandra, A., Nejentsev, S. et al. (2 more authors) (2016) PI3Kδ and primary immunodeficiencies. Nature Reviews Immunology, 16 (11). pp. 702-714. ISSN 1474-1733
Abstract
Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This is an author produced version of a paper subsequently published in Nature Reviews Immunology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Lymphocytes; Primary immunodeficiency disorders; Signal transduction |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/M012328/2 British Lung Foundation RG14-1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Jul 2016 15:09 |
Last Modified: | 10 Nov 2017 14:47 |
Published Version: | http://dx.doi.org/10.1038/nri.2016.93 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/nri.2016.93 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:102238 |