ArticleBlood2010
PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 196 citations in OpenAlex.
- First-in-human studies of seletalisib, an orally bioavailable small-molecule PI3Kδ inhibitor for the treatment of immune and inflammatory diseases.European journal of clinical pharmacology · 2017Trial
- Trial
- 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
- A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4+ T cell signaling and differentiation.The Journal of experimental medicine · 2026Article
- Defining PI3K Signaling as a Key Regulator of Molecular Heterogeneity and Inflammation in Glomerular Lupus Nephritis.Immune network · 2026Article
- IOA-244, a novel p110δ PI3K inhibitor, blocks breast tumour progression on either mono- or combined-therapy.Cell death discovery · 2026Article
- Phosphoinositide 3-kinase δ activity in patients with systemic lupus erythematosus.Frontiers in immunology · 2026Article
- Unlocking the genetic code: a comprehensive Genome-Wide association study and gene set enrichment analysis of cell-mediated immunity in chickens.BMC genomics · 2025Article
- The Mechanisms and Therapeutic Implications of PI3K Signaling in Airway Inflammation and Remodeling in Asthma.Biologics : targets & therapy · 2025Review
- Hematopoietic PI3Kδ deficiency aggravates murine atherosclerosis through impairment of Tregs.JCI insight · 2024Article
- Review
- PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis.The Journal of clinical investigation · 2024Article
- Activated phosphoinositide 3-kinase δ syndrome caused by PIK3CD mutations: expanding the phenotype.Pediatric rheumatology online journal · 2024Article
- Pan-PI3K inhibition with copanlisib overcomes Treg- and M2-TAM-mediated immune suppression and promotes anti-tumor immune responses.Clinical and experimental medicine · 2023Article
- Inhibition of PI3K p110δ activity reduces IgE production in IL-4 and anti-CD40 stimulated human B cell cultures.Immunology · 2023Article
- Stimulation of ectopically expressed muscarinic receptors induces IFN-γ but suppresses IL-2 production by inhibiting activation of pAKT pathways in primary T cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phosphatidylinositol 3-Kinase δ Deficiency Protects From Antimyeloperoxidase Vasculitis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- TNFα and IFNγ rapidly activate PI3K-AKT signaling to drive glycolysis that confers mesenchymal stem cells enhanced anti-inflammatory property.Stem cell research & therapy · 2022Article
- Design, Synthesis, and Development of Pyrazolo[1,5-Pharmaceuticals (Basel, Switzerland) · 2022Article
- Control of CD4Current topics in microbiology and immunology · 2022Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
We have previously described critical and nonredundant roles for the phosphoinositide 3-kinase p110delta during the activation and differentiation of naive T cells, and p110delta inhibitors are currently being developed for clinical use. However, to effectively treat established inflammatory or autoimmune diseases, it is important to be able to inhibit previously activated or memory T cells. In this study, using the isoform-selective inhibitor IC87114, we show that sustained p110delta activity is required for interferon-gamma production. Moreover, acute inhibition of p110delta inhibits cytokine production and reduces hypersensitivity responses in mice. Whether p110delta played a similar role in human T cells was unknown. Here we show that IC87114 potently blocked T-cell receptor-induced phosphoinositide 3-kinase signaling by both naive and effector/memory human T cells. Importantly, IC87114 reduced cytokine production by memory T cells from healthy and allergic donors and from inflammatory arthritis patients. These studies establish that previously activated memory T cells are at least as sensitive to p110delta inhibition as naive T cells and show that mouse models accurately predict p110delta function in human T cells. There is therefore a strong rationale for p110delta inhibitors to be considered for therapeutic use in T-cell-mediated autoimmune and inflammatory diseases.
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Registered trials
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.