ArticleBlood2006
Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 109 citations in OpenAlex.
- Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.PloS one · 2018Trial
- TNFAIP8 polarity proteins mediate T cell development by propagating lipid second messenger signaling in thymocytes.Cell death & disease · 2026Article
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Hepatotoxic Mechanisms of Polyethylene Terephthalate Microplastics Revealed by Network Toxicology, Molecular Docking, and In Vivo Validation.International journal of molecular sciences · 2026Article
- T Cell-Specific Inactivation of the PI3K p110α Catalytic Subunit: Effect in T Cell Differentiation and Antigen-Specific Responses.International journal of molecular sciences · 2025Article
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.Science translational medicine · 2023Article
- Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF.Nature immunology · 2023Article
- Class I PI3K regulatory subunits control differentiation of dendritic cell subsets and regulate Flt3L mediated signal transduction.Scientific reports · 2022Article
- A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1-mediated adhesion in T cells.Science signaling · 2022Article
- Therapeutic inhibition of the SRC-kinase HCK facilitates T cell tumor infiltration and improves response to immunotherapy.Science advances · 2022Article
- PI3K Isoforms in Vascular Biology, A Focus on the Vascular System-Immune Response Connection.Current topics in microbiology and immunology · 2022Article
- PI3K Isoforms in CD8Current topics in microbiology and immunology · 2022Article
- Control of CD4Current topics in microbiology and immunology · 2022Article
- Metabolic regulation of T cell development.Frontiers in immunology · 2022Review
- Review
- Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity.Acta pharmacologica Sinica · 2020Review
- Mitochondrial Pyruvate Carrier 1 Promotes Peripheral T Cell Homeostasis through Metabolic Regulation of Thymic Development.Cell reports · 2020Article
- The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia.Cold Spring Harbor perspectives in medicine · 2020Review
- RRAS2 shapes the TCR repertoire by setting the threshold for negative selection.The Journal of experimental medicine · 2019Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Class 1 phosphoinositide 3-kinases (PI3Ks), consisting of PI3Kalpha, beta, gamma, and delta, are a family of intracellular signaling molecules that play important roles in cell-mediated immune responses. In thymocytes, however, their role is less clear, although PI3Kgamma is postulated to partially contribute to pre-TCR-dependent differentiation. We now report that PI3Kdelta, in conjunction with PI3Kgamma, is required for thymocyte survival and ultimately for T-cell production. Surprisingly, genetic deletion of the p110delta and p110gamma catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of corticomedullary differentiation. Total thymocyte counts in these animals were 27-fold lower than in wild-type (WT) controls because of a diminished number of CD4+ CD8+ double-positive (DP) cells and were associated with T-cell depletion in blood and in secondary lymphoid organs. Moreover, this alteration in the DP population was intrinsic to thymocytes, because the reconstitution of p110gammadelta-/- animals with WT fetal liver cells restored the proportions of all thymocyte populations to those in WT controls. The observed defects were related to massive apoptosis in the DP population; TCRB expression, pre-TCR selection, and generation of DP cells appeared relatively unperturbed. Thus, class 1 PI3Ks work in concert to protect developing thymocytes from apoptosis.
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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.