ArticleThe Journal of clinical investigation2024
S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.Science advances · 2026Article
- S1P-S1PR1 signaling impairs CD8EMBO reports · 2026Article
- S1PR1 signaling biases neutrophils toward long-lived low-inflammatory functional states.bioRxiv : the preprint server for biology · 2026Article
- The emerging role of SPHK1 at the immune-metabolic interface: a pan-cancer integrative analysis.Scientific reports · 2026Article
- Genome-wide Association Studies of the Pathogenic Sphingosine-1-Phosphate Gene in Ulcerative ColitisEndocrine, metabolic & immune disorders drug targets · 2026Article
- Sphingolipid Metabolism in the Pathogenesis of Hashimoto's Thyroiditis.International journal of molecular sciences · 2025Review
- In situ-formed immunotherapeutic hydrogel containing sphingosine-1-phosphate for enhanced lung cancer immunotherapy.Science advances · 2025Article
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- PD-1 expressing islet-specific CD4Immunology and cell biology · 2025Article
- Reconstitution of T cell-mediated immunity by umbilical cord-derived mesenchymal stem cells in ulcerative colitis.Clinical and translational medicine · 2025Article
- ATP11B triggers the infiltration of T cells into GBM and intensifies anti-GBM immunity by upregulating and externalizing S1PR1.Journal of translational medicine · 2025Article
- Exploratory analyses of leukocyte responses in hospitalized patients treated with ozanimod following a severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection.Immunology and cell biology · 2025Article
- Aberrant T follicular helper cells generated by TNature immunology · 2025Article
- Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.Cell & bioscience · 2025Article
- Modulating lipid metabolism improves tumor immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Article
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Discovery of Potent, Orally Bioavailable Sphingosine-1-Phosphate Transporter (Spns2) Inhibitors.Journal of medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Effective immunity requires a large, diverse naive T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we addressed how S1P enables T cell survival and the implications for patients treated with S1PR1 antagonists. We found that S1PR1 limited apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization were required to prevent this proapoptotic cascade. Findings in mice were recapitulated in ulcerative colitis patients treated with the S1PR1 antagonist ozanimod, and the loss of naive T cells limited B cell responses. Our findings highlighted an effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress, and suggested both limitations and additional uses of this important class of drugs.
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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.