ArticleThe Journal of experimental medicine2010
Thymic development beyond beta-selection requires phosphatidylinositol 3-kinase activation by CXCR4.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 143 citations in OpenAlex.
- Epithelial chemokine CCL25 integrates T cell development and intestinal homeostasis.The Journal of experimental medicine · 2026Article
- WHIM syndrome in a child without the classic tetrad: a case confirmed by de novo CXCR4 mutation.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 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
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Optimizing in vitro T cell differentiation by using induced pluripotent stem cells with GFP-RUNX1 and mCherry-TCF7 labelling.Cell proliferation · 2024Article
- Severe CD8+ T Lymphopenia in WHIM Syndrome Caused by Selective Sequestration in Primary Immune Organs.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Review
- E-cadherin in developing murine T cells controls spindle alignment and progression through β-selection.Science advances · 2023Article
- Diversity in Cortical Thymic Epithelial Cells Occurs through Loss of a Foxn1-Dependent Gene Signature Driven by Stage-Specific Thymocyte Cross-Talk.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Review
- The significance of the SDF-1/CXCR4 signaling pathway in the normal development.Molecular biology reports · 2022Review
- Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development.NPJ Regenerative medicine · 2022Article
- Metabolic regulation of T cell development.Frontiers in immunology · 2022Review
- Review
- Developing T cells form an immunological synapse for passage through the β-selection checkpoint.The Journal of cell biology · 2021Article
- A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy.Nature communications · 2021Article
- PI3K in T Cell Adhesion and Trafficking.Frontiers in immunology · 2021Review
- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Pleiotropic Roles of VEGF in the Microenvironment of the Developing Thymus.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity.Acta pharmacologica Sinica · 2020Review
24 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
6 authors at 3 institutions in 3 countries.
Funding
Abstract
T cell development requires phosphatidylinositol 3-kinase (PI3K) signaling with contributions from both the class IA, p110delta, and class IB, p110gamma catalytic subunits. However, the receptors on immature T cells by which each of these PI3Ks are activated have not been identified, nor has the mechanism behind their functional redundancy in the thymus. Here, we show that PI3K signaling from the preTCR requires p110delta, but not p110gamma. Mice deficient for the class IB regulatory subunit p101 demonstrated the requirement for p101 in T cell development, implicating G protein-coupled receptor signaling in beta-selection. We found evidence of a role for CXCR4 using small molecule antagonists in an in vitro model of beta-selection and demonstrated a requirement for CXCR4 during thymic development in CXCR4-deficient embryos. Finally, we demonstrate that CXCL12, the ligand for CXCR4, allows for Notch-dependent differentiation of DN3 thymocytes in the absence of supporting stromal cells. These findings establish a role for CXCR4-mediated PI3K signaling that, together with signals from Notch and the preTCR, contributes to continued T cell development beyond beta-selection.
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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.