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Cited by 342Immunodeficiency and Autoimmune DisordersT-cell and B-cell ImmunologyPI3K/AKT/mTOR signaling in cancer

PI3Kδ and primary immunodeficiencies

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Lucas, Carrie L., Chandra, Anita, Nejentsev, Sergey, Condliffe, Alison M., Okkenhaug, Klaus·2016·Nature Reviews Immunology
DOI 10.1038/nri.2016.93PMC PMC5291318
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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.

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References 93 · Cited by 342

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Authors
Lucas, C. L., Chandra, A., Nejentsev, S., Condliffe, A. M., & Okkenhaug, K.
Affiliations
  • National Institutes of Health (US)
  • Babraham Institute (GB)
  • University of Cambridge (GB)
  • University of Sheffield (GB)
Corresponding author
Okkenhaug, Klaus
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2016-09-12
Volume
16
Issue
11
Pages
702-714
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/nri.2016.93
PMC
PMC5291318
OpenAlex
W2512972788
Cited by
342
References
93
Citations by year
2026: 26 · 2025: 36 · 2024: 33 · 2023: 32 · 2022: 37 · 2021: 38 · 2020: 34 · 2019: 30 · 2018: 52 · 2017: 23 · 2016: 1
FWCI
3.41
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Apollo
Funders
  • GlaxoSmithKline
  • Yale University
  • Wellcome Trust (103413/Z/13/Z, 095691/Z/11/Z)
  • National Institute for Health and Care Research
  • British Lung Foundation (K99/R00)
  • European Commission (261441)
  • National Institutes of Health (K99-R00, UL1TR001863)
  • Medical Research Council (MR/M012328/2, MR/M012328/1, MR/M012328, EU FP7)
  • Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0407, BBS/E/B/0000H329, BBS/E/B/000C0409)
  • NIHR Cambridge Biomedical Research Centre
  • National Heart, Lung, and Blood Institute
  • National Institute of Allergy and Infectious Diseases
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
PI3Kδ, phosphatidylinositol 3-kinase, primary immunodeficiency, gain-of-function mutations, loss-of-function mutations, PIK3CD, PIK3R1, adaptive immunity, lymphocyte development, immunosuppression, senescent T cells, lymphadenopathy
MeSH terms
Phosphoinositide-3 Kinase Inhibitors, Animals, Cell Differentiation, Enzyme Activation, Gene Expression Regulation, Humans, Immune System, Immunity, Immunologic Deficiency Syndromes, Lymphocyte Activation, Lymphocytes, Mutation, Signal Transduction, Cellular Senescence, Phosphatidylinositol 3-Kinases, Protein Subunits, Molecular Targeted Therapy

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