Activating mutations in PIK3CD disrupt the differentiation and function of human and murine CD4

Animals CD4-Positive T-Lymphocytes / metabolism Cell Differentiation Cytokines / metabolism Gain of Function Mutation Humans Mice Phenotype Phosphatidylinositol 3-Kinases / genetics
CD4(+) T-cell function PIK3CD Phosphoinositide 3-kinase activated PI3Kδ syndrome follicular helper T cells humans humoral immunity immune class regulation mouse models

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
07 2019
Historique:
received: 03 09 2018
revised: 21 12 2018
accepted: 17 01 2019
pubmed: 10 2 2019
medline: 19 5 2020
entrez: 10 2 2019
Statut: ppublish

Résumé

Gain-of-function (GOF) mutations in PIK3CD cause a primary immunodeficiency characterized by recurrent respiratory tract infections, susceptibility to herpesvirus infections, and impaired antibody responses. Previous work revealed defects in CD8 We sought to dissect the effects of increased phosphoinositide 3-kinase (PI3K) signaling on CD4 We performed detailed ex vivo, in vivo, and in vitro phenotypic and functional analyses of patients' CD4 PI3K overactivation caused substantial increases in numbers of memory and follicular helper T (T Our studies reveal that CD4

Sections du résumé

BACKGROUND
Gain-of-function (GOF) mutations in PIK3CD cause a primary immunodeficiency characterized by recurrent respiratory tract infections, susceptibility to herpesvirus infections, and impaired antibody responses. Previous work revealed defects in CD8
OBJECTIVE
We sought to dissect the effects of increased phosphoinositide 3-kinase (PI3K) signaling on CD4
METHODS
We performed detailed ex vivo, in vivo, and in vitro phenotypic and functional analyses of patients' CD4
RESULTS
PI3K overactivation caused substantial increases in numbers of memory and follicular helper T (T
CONCLUSION
Our studies reveal that CD4

Identifiants

DOI: 10.1016/j.jaci.2019.01.033 PMID: 30738173 PMC: PMC6612302
pubmed: 30738173
pii: S0091-6749(19)30192-7
doi: 10.1016/j.jaci.2019.01.033
pmc: PMC6612302
mid: NIHMS1520992
pii:
doi:

Substances chimiques

Cytokines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

236-253

Subventions

Organisme : Intramural NIH HHS
ID : Z99 AI999999
Pays : United States

Informations de copyright

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.

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Auteurs

Julia Bier (J)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.

Geetha Rao (G)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia.

Kathryn Payne (K)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia.

Henry Brigden (H)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; University of Bath, Bath, United Kingdom.

Elise French (E)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; University of Bath, Bath, United Kingdom.

Simon J Pelham (SJ)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.

Anthony Lau (A)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.

Helen Lenthall (H)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia.

Emily S J Edwards (ESJ)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.

Joanne M Smart (JM)

Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Melbourne, Australia.

Theresa S Cole (TS)

Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Melbourne, Australia.

Sharon Choo (S)

Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Melbourne, Australia.

Avni Y Joshi (AY)

Division of Allergy and Immunology, Mayo Clinic Children's Center, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minn.

Roshini S Abraham (RS)

Division of Allergy and Immunology, Mayo Clinic Children's Center, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minn; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.

Michael O'Sullivan (M)

Department of Immunology and Allergy, Princess Margaret Hospital, Subiaco, Australia.

Kaan Boztug (K)

Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; St Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Isabelle Meyts (I)

Department of Immunology and Microbiology, Childhood Immunology, Department of Pediatrics, University Hospitals Leuven and KU Leuven, Leuven, Belgium.

Paul E Gray (PE)

School of Women's and Children's Health, University of New South Wales, Sydney, Australia; Clinical Immunogenomics Research Consortia Australia, Sydney, Australia.

Lucinda J Berglund (LJ)

Clinical Immunogenomics Research Consortia Australia, Sydney, Australia; Immunopathology Department, Westmead Hospital, Westmead, Australia; Faculty of Medicine, University of Sydney, Sydney, Australia.

Peter Hsu (P)

Clinical Immunogenomics Research Consortia Australia, Sydney, Australia; Faculty of Medicine, University of Sydney, Sydney, Australia; Children's Hospital at Westmead, Westmead, Australia.

Melanie Wong (M)

Clinical Immunogenomics Research Consortia Australia, Sydney, Australia; Faculty of Medicine, University of Sydney, Sydney, Australia; Children's Hospital at Westmead, Westmead, Australia.

Steven M Holland (SM)

Laboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

Luigi D Notarangelo (LD)

Laboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

Gulbu Uzel (G)

Laboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

Cindy S Ma (CS)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; Clinical Immunogenomics Research Consortia Australia, Sydney, Australia.

Robert Brink (R)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; Clinical Immunogenomics Research Consortia Australia, Sydney, Australia.

Stuart G Tangye (SG)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; Clinical Immunogenomics Research Consortia Australia, Sydney, Australia. Electronic address: s.tangye@garvan.org.au.

Elissa K Deenick (EK)

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; Clinical Immunogenomics Research Consortia Australia, Sydney, Australia. Electronic address: e.deenick@garvan.org.au.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD4+ › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation gain de fonction › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Activating mutations in PIK3CD disrupt the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › Activating mutations in PIK3CD disrupt the...