ArticleJournal of immunology (Baltimore, Md. : 1950)2012
The role of sphingosine-1-phosphate transporter Spns2 in immune system function.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 98 citations in OpenAlex.
- DHCR24 regulates endothelial senescence through the SPHK2/SPNS2-S1P axis.Biogerontology · 2026Article
- Sex hormones influence ORMDL3 expression: Implications for sex-associated asthma phenotype.The Journal of allergy and clinical immunology · 2026Article
- Fingolimod Prevents Neuroinflammation but Has a Limited Effect on the Development of Ataxia in a Mouse Model for SCA1.International journal of molecular sciences · 2025Article
- Assessment of Spinster homologue 2 (Spns2)-dependent transport of sphingosine-1-phosphate as a therapeutic target.British journal of pharmacology · 2025Article
- Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice.Biomolecules & therapeutics · 2025Article
- Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.International journal of molecular sciences · 2025Review
- Discovery of Potent, Orally Bioavailable Sphingosine-1-Phosphate Transporter (Spns2) Inhibitors.Journal of medicinal chemistry · 2024Article
- Leveraging altered lipid metabolism in treating B cell malignancies.Progress in lipid research · 2024Review
- Spinster Homologue 2 Expression Correlates With Improved Patient Survival in Hepatocellular Carcinoma Despite Association With Lymph-Angiogenesis.World journal of oncology · 2024Article
- Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.Frontiers in immunology · 2024Review
- Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.EMBO reports · 2023Article
- The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Structural and functional insights into Spns2-mediated transport of sphingosine-1-phosphate.Cell · 2023Article
- 2-Aminobenzoxazole Derivatives as Potent Inhibitors of the Sphingosine-1-Phosphate Transporter Spinster Homolog 2 (Spns2).Journal of medicinal chemistry · 2023Article
- Immunosenescence and inflamm-ageing in COVID-19.Ageing research reviews · 2023Review
- Proton-driven alternating access in a spinster lipid transporter.Nature communications · 2022Article
- Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors.Journal of medicinal chemistry · 2022Article
- Keep a Little Fire Burning-The Delicate Balance of Targeting Sphingosine-1-Phosphate in Cancer Immunity.International journal of molecular sciences · 2022Review
- Review
- Role of Sphingolipids in Multiple Myeloma Progression, Drug Resistance, and Their Potential as Therapeutic Targets.Frontiers in oncology · 2022Review
8 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
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, immune system functions, and many other physiological processes. However, the mechanisms of S1P transport across cellular membranes remain poorly understood, with several ATP-binding cassette family members and the spinster 2 (Spns2) member of the major facilitator superfamily known to mediate S1P transport in cell culture. Spns2 was also shown to control S1P activities in zebrafish in vivo and to play a critical role in zebrafish cardiovascular development. However, the in vivo roles of Spns2 in mammals and its involvement in the different S1P-dependent physiological processes have not been investigated. In this study, we characterized Spns2-null mouse line carrying the Spns2(tm1a(KOMP)Wtsi) allele (Spns2(tm1a)). The Spns2(tm1a/tm1a) animals were viable, indicating a divergence in Spns2 function from its zebrafish ortholog. However, the immunological phenotype of the Spns2(tm1a/tm1a) mice closely mimicked the phenotypes of partial S1P deficiency and impaired S1P-dependent lymphocyte trafficking, with a depletion of lymphocytes in circulation, an increase in mature single-positive T cells in the thymus, and a selective reduction in mature B cells in the spleen and bone marrow. Spns2 activity in the nonhematopoietic cells was critical for normal lymphocyte development and localization. Overall, Spns2(tm1a/tm1a) resulted in impaired humoral immune responses to immunization. This study thus demonstrated a physiological role for Spns2 in mammalian immune system functions but not in cardiovascular development. Other components of the S1P signaling network are investigated as drug targets for immunosuppressive therapy, but the selective action of Spns2 may present an advantage in this regard.
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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.