ArticlePLoS pathogens2014
Neutral sphingomyelinase in physiological and measles virus induced T cell suppression.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Sphingolipids associate with the chlamydial nucleoid and mark developmental transitions in Chlamydia trachomatis.Nature communications · 2026Article
- Measles virus reprograms CD4Frontiers in cell and developmental biology · 2026Article
- Article
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.International journal of molecular sciences · 2024Article
- Article
- Sphingomyelin Depletion Inhibits CXCR4 Dynamics and CXCL12-Mediated Directed Cell Migration in Human T Cells.Frontiers in immunology · 2022Article
- Review
- Ceramide and Related Molecules in Viral Infections.International journal of molecular sciences · 2021Review
- Measles immunity and immunosuppression.Current opinion in virology · 2021Review
- The Manifold Roles of Sphingolipids in Viral Infections.Frontiers in physiology · 2021Review
- Unbalanced Sphingolipid Metabolism and Its Implications for the Pathogenesis of Psoriasis.Molecules (Basel, Switzerland) · 2020Review
- Neutral Sphingomyelinase-2 (NSM 2) Controls T Cell Metabolic Homeostasis and Reprogramming During Activation.Frontiers in molecular biosciences · 2020Article
- Translational Approaches Targeting Ceramide Generation From Sphingomyelin in T Cells to Modulate Immunity in Humans.Frontiers in immunology · 2019Review
- Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen.Frontiers in cell and developmental biology · 2019Review
- Review: Bioengineering strategies to probe T cell mechanobiology.APL bioengineering · 2018Review
- Editorial: Membrane Lipids in T Cell Functions.Frontiers in immunology · 2018Article
- The Neutral Sphingomyelinase 2 Is Required to Polarize and Sustain T Cell Receptor Signaling.Frontiers in immunology · 2018Article
- Measles Virus Enters Breast and Colon Cancer Cell Lines through a PVRL4-Mediated Macropinocytosis Pathway.Journal of virology · 2017Article
- The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis.Journal of virology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell paralysis is a main feature of measles virus (MV) induced immunosuppression. MV contact mediated activation of sphingomyelinases was found to contribute to MV interference with T cell actin reorganization. The role of these enzymes in MV-induced inhibition of T cell activation remained equally undefined as their general role in regulating immune synapse (IS) activity which relies on spatiotemporal membrane patterning. Our study for the first time reveals that transient activation of the neutral sphingomyelinase 2 (NSM2) occurs in physiological co-stimulation of primary T cells where ceramide accumulation is confined to the lamellum (where also NSM2 can be detected) and excluded from IS areas of high actin turnover. Genetic ablation of the enzyme is associated with T cell hyper-responsiveness as revealed by actin dynamics, tyrosine phosphorylation, Ca2+-mobilization and expansion indicating that NSM2 acts to suppress overshooting T cell responses. In line with its suppressive activity, exaggerated, prolonged NSM2 activation as occurring in co-stimulated T cells following MV exposure was associated with aberrant compartmentalization of ceramides, loss of spreading responses, interference with accumulation of tyrosine phosphorylated protein species and expansion. Altogether, this study for the first time reveals a role of NSM2 in physiological T cell stimulation which is dampening and can be abused by a virus, which promotes enhanced and prolonged NSM2 activation to cause pathological T cell suppression.
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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.