ArticlePloS one2012
Age-dependent changes in the sphingolipid composition of mouse CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Plasma lipids connecting olfaction with cognition and physical function.Scientific reports · 2026Article
- Sphingolipid biosynthesis is essential for metabolic rewiring during TScience advances · 2024Article
- Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand.Frontiers in immunology · 2023Article
- The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease.Biomedicines · 2022Review
- Sickle cell disease as an accelerated aging syndrome.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Lipids as Regulators of Cellular Senescence.Frontiers in physiology · 2022Review
- Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans.Nature communications · 2021Article
- LXR directly regulates glycosphingolipid synthesis and affects human CD4+ T cell function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The importance of age in compositional and functional profiling of the human intestinal microbiome.PloS one · 2021Article
- Multiple genetic programs contribute to CD4 T cell memory differentiation and longevity by maintaining T cell quiescence.Cellular immunology · 2020Article
- 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
- Emerging roles for sphingolipids in cellular aging.Current genetics · 2018Review
- Role of sphingolipids in senescence: implication in aging and age-related diseases.The Journal of clinical investigation · 2018Review
- Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells.Molecular biology of the cell · 2017Article
- Autophagy regulates sphingolipid levels in the liver.Journal of lipid research · 2014Article
- Effect of procysteine on aging-associated changes in hepatic GSH and SMase: evidence for transcriptional regulation of smpd3.Journal of lipid research · 2014Article
- Sphingolipids and lifespan regulation.Biochimica et biophysica acta · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4(+) T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4(+) T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4(+) T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4(+) T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4(+) T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4(+) T cell function.
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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.