ArticleProceedings of the National Academy of Sciences of the United States of America2016
The actin cytoskeleton modulates the activation of iNKT cells by segregating CD1d nanoclusters on antigen-presenting cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. 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, 36 citations in OpenAlex.
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- Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The cortical actin network regulates avidity-dependent binding of hyaluronan by the lymphatic vessel endothelial receptor LYVE-1.The Journal of biological chemistry · 2020Article
- Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells.Frontiers in immunology · 2020Review
- Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Hepatocellular cancer-derived alpha fetoprotein uptake reduces CD1 molecules on monocyte-derived dendritic cells.Cellular immunology · 2019Article
- Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae.Nature communications · 2018Article
- Microdomain formation is a general property of bacterial membrane proteins and induces heterogeneity of diffusion patterns.BMC biology · 2018Article
- Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A.Science signaling · 2018Article
- Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis.Immunology · 2018Review
- Immunometabolic Activation of Invariant Natural Killer T Cells.Frontiers in immunology · 2018Review
- CD1-Restricted T Cells During Persistent Virus Infections: "Sympathy for the Devil".Frontiers in immunology · 2018Review
- N-glycan mediated adhesion strengthening during pathogen-receptor binding revealed by cell-cell force spectroscopy.Scientific reports · 2017Article
- Ergodicity breaking on the neuronal surface emerges from random switching between diffusive states.Scientific reports · 2017Article
- ATP Binding Cassette Transporter ABCA7 Regulates NKT Cell Development and Function by Controlling CD1d Expression and Lipid Raft Content.Scientific reports · 2017Article
- Harnessing the Power of Invariant Natural Killer T Cells in Cancer Immunotherapy.Frontiers in immunology · 2017Review
- Development of nanoscale structure in LAT-based signaling complexes.Journal of cell science · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Invariant natural killer T (iNKT) cells recognize endogenous and exogenous lipid antigens presented in the context of CD1d molecules. The ability of iNKT cells to recognize endogenous antigens represents a distinct immune recognition strategy, which underscores the constitutive memory phenotype of iNKT cells and their activation during inflammatory conditions. However, the mechanisms regulating such "tonic" activation of iNKT cells remain unclear. Here, we show that the spatiotemporal distribution of CD1d molecules on the surface of antigen-presenting cells (APCs) modulates activation of iNKT cells. By using superresolution microscopy, we show that CD1d molecules form nanoclusters at the cell surface of APCs, and their size and density are constrained by the actin cytoskeleton. Dual-color single-particle tracking revealed that diffusing CD1d nanoclusters are actively arrested by the actin cytoskeleton, preventing their further coalescence. Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton and correlates with enhanced iNKT cell activation. Importantly and consistently with iNKT cell activation during inflammatory conditions, exposure of APCs to the Toll-like receptor 7/8 agonist R848 increases nanocluster density and iNKT cell activation. Overall, these results define a previously unidentified mechanism that modulates iNKT cell autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d nanoclusters.
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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.