ArticleEuropean journal of immunology2013
PI3Kγ kinase activity is required for optimal T-cell activation and differentiation.
Article in European journal of immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.Frontiers in immunology · 2022Pooled it
- Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells.Journal of leukocyte biology · 2015Trial
- CAR-T cells with the CD38Cell reports. Medicine · 2026Article
- High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways.Science advances · 2025Article
- Galangin reduces MPTP-induced dopamine neuron injury via the autophagy dependent-PI3K/AKT pathway.Frontiers in aging neuroscience · 2025Article
- Tuning spacer length improves the functionality of the nanobody-based VEGFR2 CAR T cell.BMC biotechnology · 2024Article
- Optimizing single cell proteomics using trapped ion mobility spectrometry for label-free experiments.The Analyst · 2023Article
- The role of PI3Kγ in the immune system: new insights and translational implications.Nature reviews. Immunology · 2022Review
- Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity.Acta pharmaceutica Sinica. B · 2022Article
- Extranodal Natural Killer/T-Cell Lymphomas: Current Approaches and Future Directions.Journal of clinical medicine · 2022Review
- PI3K Isoforms in CD8Current topics in microbiology and immunology · 2022Article
- High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach.Journal of personalized medicine · 2021Article
- Identification and Characterization of the Amphioxus Lck and Its Associated Tyrosine Phosphorylation-Dependent Inhibitory LRR Receptor.Frontiers in immunology · 2021Article
- Immunological characterization of HM5023507, an orally active PI3Kδ/γ inhibitor.Pharmacology research & perspectives · 2020Article
- Multifunctional cytokine production reveals functional superiority of memory CD4 T cells.European journal of immunology · 2019Article
- Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology.Nature communications · 2019Article
- Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study.American journal of hematology · 2018Article
- PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer.Oncology letters · 2018Article
- Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection.FEBS letters · 2017Article
- The Selective Phosphoinoside-3-Kinase p110δ Inhibitor IPI-3063 Potently Suppresses B Cell Survival, Proliferation, and Differentiation.Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol-3-kinase gamma (PI3Kγ) is a leukocyte-specific lipid kinase with signaling function downstream of G protein-coupled receptors to regulate cell trafficking, but its role in T cells remains unclear. To investigate the requirement of PI3Kγ kinase activity in T-cell function, we studied T cells from PI3Kγ kinase-dead knock-in (PI3Kγ(KD/KD)) mice expressing the kinase-inactive PI3Kγ protein. We show that CD4(+) and CD8(+) T cells from PI3Kγ(KD/KD) mice exhibit impaired TCR/CD28-mediated activation that could not be rescued by exogenous IL-2. The defects in proliferation and cytokine production were also evident in naïve and memory T cells. Analysis of signaling events in activated PI3Kγ(KD/KD) T cells revealed a reduction in phosphorylation of protein kinase B (AKT) and ERK1/2, a decrease in lipid raft formation, and a delay in cell cycle progression. Furthermore, PI3Kγ(KD/KD) CD4(+) T cells displayed compromised differentiation toward Th1, Th2, Th17, and induced Treg cells. PI3Kγ(KD/KD) mice also exhibited an impaired response to immunization and a reduced delayed-type hypersensitivity to Ag challenge. These findings indicate that PI3Kγ kinase activity is required for optimal T-cell activation and differentiation, as well as for mounting an efficient T cell-mediated immune response. The results suggest that PI3Kγ kinase inhibitors could be beneficial in reducing the undesirable immune response in autoimmune diseases.
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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.