ArticleNature immunology2018
Hyperactivated PI3Kδ promotes self and commensal reactivity at the expense of optimal humoral immunity.
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Article in Nature immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
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64citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% of its field
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review.Clinical reviews in allergy & immunology · 2020Pooled it
- Trial
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Distributed clonal deletion prevents autoimmune disease progression.Cell reports · 2026Article
- Activated PIK3CD drives marginal zone B cell development from early transitional progenitors by enhancing ADAM10 expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4+ T cell signaling and differentiation.The Journal of experimental medicine · 2026Article
- Phosphoinositide 3-kinase δ activity in patients with systemic lupus erythematosus.Frontiers in immunology · 2026Article
- PI3Kdelta-driven expansion of regulatory B cells impairs protective immune responses to Trypanosoma congolense parasite infection.PLoS pathogens · 2025Article
- PI3K GOF leads to dysregulation of T and B cells that both contribute to extrinsically driving activation and differentiation of other CD4Immunology and cell biology · 2025Article
- Article
- Review
- Review
- Activated PI3Kδ syndrome in inborn errors of immunity: diagnostic strategies and clinical challenges.Frontiers in immunology · 2025Observational
- Activated phosphoinositide 3-kinase delta syndrome: Pathogenesis, clinical manifestations, and treatment.Pediatric discovery · 2024Review
- Activated PI3Kδ Specifically Perturbs Mouse Regulatory T Cell Homeostasis and Function Leading to Immune Dysregulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Phenotypic and Immunological Characterization of Patients with Activated PI3Kδ Syndrome 1 Presenting with Autoimmunity.Journal of clinical immunology · 2024Article
- Failed Downregulation of PI3K Signaling Makes Autoreactive B Cells Receptive to Bystander T Cell Help.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Interim analysis: Open-label extension study of leniolisib for patients with APDS.The Journal of allergy and clinical immunology · 2024Article
- Activated PI3Kδ specifically perturbs mouse Treg homeostasis and function leading to immune dysregulation.bioRxiv : the preprint server for biology · 2023Article
- Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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Authors and funding
23 authors at 4 institutions in 2 countries.
Silvia PreiteNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. silvia.preite@nih.gov.ORCID http://orcid.org/0000-0002-0122-1142
Jennifer L CannonsNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Andrea J RadtkeLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ivan Vujkovic-CvijinLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Julio Gomez-RodriguezNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Stefano VolpiClinica Pediatrica e Reumatologia, Centro per le Malattie Autoinfiammatorie e Immunodeficienze, Istituto Giannina Gaslini, Genoa, Italy.ORCID http://orcid.org/0000-0002-7129-868X
Bonnie HuangNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Jun ChengNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Nicholas CollinsLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Julie ReilleyNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Robin HandonNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Kerry DobbsLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3432-3137
Lutfi HuqLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Indu RamanMicroarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Chengsong ZhuMicroarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Quan-Zhen LiMicroarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ming O LiImmunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Stefania PittalugaLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Gulbu UzelLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8335-0262
Yasmine BelkaidLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ronald N GermainLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Pamela L SchwartzbergNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. pams@mail.nih.gov.ORCID http://orcid.org/0000-0001-6318-9187
National Institutes of Health · USThe University of Texas Southwestern Medical Center · USIstituto Giannina Gaslini · ITMemorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MMultiscale Analysis of Immune ResponsesZIAAI000545 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GERMAIN, RONALD N · 2009 to 2025
$29.4MNHGRI/DIR Embryonic Stem Cell and Transgenic Mouse CoreZICHG200349 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BURGESS, SHAWN M · 2010 to 2025
$23.8MRole of the microbiota in immunityZIAAI001115 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2009 to 2025
$22.4MGenetic and Biochemical Approaches to Tyrosine Kinase FunctionZIAHG000123 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SCHWARTZBERG, PAMELA · 2009 to 2018
$20.8MNIAID Microbiome ProgramZICAI001233 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOUTSOPOULOS, NIKI · 2018 to 2025
$18.9MGenetic and Biochemical Approaches to Tyrosine Kinase and Lymphocyte SignalingZIAAI001240 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHWARTZBERG, PAMELA · 2019 to 2025
$18.8MCharacterization of the cellular and molecular bases of inborn errors of immunityZIAAI001222 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2017 to 2025
$15.2MNutrient Sensing and mTORC1 Signaling in the Control of Regulatory T Cell Generation and FunctionR01AI102888 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI LI, MING · 2014 to 2022
$4.3MIntramural NIH HHS ZIA HG000123NCI NIH HHS P30 CA008748NIAID NIH HHS R01 AI102888
Abstract
Gain-of-function mutations in the gene encoding the phosphatidylinositol-3-OH kinase catalytic subunit p110δ (PI3Kδ) result in a human primary immunodeficiency characterized by lymphoproliferation, respiratory infections and inefficient responses to vaccines. However, what promotes these immunological disturbances at the cellular and molecular level remains unknown. We generated a mouse model that recapitulated major features of this disease and used this model and patient samples to probe how hyperactive PI3Kδ fosters aberrant humoral immunity. We found that mutant PI3Kδ led to co-stimulatory receptor ICOS-independent increases in the abundance of follicular helper T cells (T
Indexed as
AnimalsAutoantibodiesB-LymphocytesCells, CulturedClass I Phosphatidylinositol 3-KinasesDisease Models, AnimalForkhead Box Protein O1Gastrointestinal MicrobiomeGerminal CenterHumansImmunity, HumoralImmunoglobulin Class SwitchingImmunologic Deficiency SyndromesMiceMice, Inbred C57BLMice, TransgenicAutoantibodiesClass I Phosphatidylinositol 3-KinasesForkhead Box Protein O1Phosphatidylinositol 3-KinasesPIK3CD protein, humanPik3cd protein, mouseProto-Oncogene Proteins c-bcl-2
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.