ArticleThe Journal of experimental medicine2009
T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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Who cites it
189 citing papers in PubMed, 324 citations in OpenAlex.
- Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo.Clinical and experimental immunology · 2015Trial
- Triple-Frequency Electromagnetic Stimulation Combined with Fingolimod Reduces Breast Cancer Cell Proliferation and Metastasis-Associated Extracellular Vesicle Protein Levels.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Decoding the S1P-S1PR axis in cancer: Mechanisms, pathways and therapeutic horizons (Review).Biomedical reports · 2026Review
- Inducible T-bet deletion reveals tissue-specific requirements in NKp46+ ILC immunobiology and response to murine cytomegalovirus.Nature communications · 2026Article
- Clinicopathologic implications of sphingosine-1-phosphate pathway in extranodal NK/T-cell lymphoma according to immune subtype.Scientific reports · 2026Article
- Sphingosine-1-Phosphate-derived 2-Hexadecenal is a central mediator of ocular neovascularization by inhibiting Sphingosine-1-Phosphate receptor 5.Nature communications · 2026Article
- Intratumoral TScience immunology · 2026Article
- Review
- Transcriptional networks weaving natural killer anti-tumor immune response.Molecular cancer · 2026Review
- T-bet Fate Mapping Reveals Gestational Stage-Specific Transcriptional Adaptation of Decidual NK Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Sphingosine-1-Phosphate Regulation to Alleviate Sickle Cell Disease Severity: A Promising Therapeutic Approach.Saudi medical journal · 2026Review
- Sphingosine-1-Phosphate Receptor 5 Signaling Is Redundant in Preclinical Models of Inflammatory Bowel Disease.Cellular and molecular gastroenterology and hepatology · 2026Article
- Targeting SPHK1 in macrophages remodels the tumor microenvironment and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer liver metastasis.Cancer communications (London, England) · 2025Article
- Two-stage CD8Nature communications · 2025Article
- Intrathymic Cell Migration: Implications in Thymocyte Development and T Lymphocyte Repertoire Formation.Advances in experimental medicine and biology · 2025Review
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Unique pharmacological properties of etrasimod among S1P receptor modulators.FEBS open bio · 2025Article
- Unraveling the complexity of ulcerative colitis: insights into cytokine dysregulation and targeted therapies.EXCLI journal · 2025Review
- Sphingosine 1-phosphate receptor 1 modulators exert neuroprotective effects in central nervous system disorders.Frontiers in pharmacology · 2025Review
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified a strain, designated Duane, in which NK cells were reduced in blood and spleen but increased in lymph nodes (LNs) and bone marrow (BM). The accumulation of NK cells in LNs reflected a decreased ability to exit into lymph. This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein. Duane NK cells have a 30-fold deficiency in sphingosine-1-phosphate receptor 5 (S1P5) transcript levels, and S1P5-deficient mice exhibit an egress defect similar to Duane. Chromatin immunoprecipitation confirms binding of T-bet to the S1pr5 locus. S1P-deficient mice exhibit a more severe NK cell egress block, and the FTY720-sensitive S1P1 also plays a role in NK cell egress from LNs. S1P5 is not inhibited by CD69, a property that may facilitate trafficking of activated NK cells to effector sites. Finally, the accumulation of NK cells within BM of S1P-deficient mice was associated with reduced numbers in BM sinusoids, suggesting a role for S1P in BM egress. In summary, these findings identify S1P5 as a T-bet-induced gene that is required for NK cell egress from LNs and BM.
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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.