Evidence map›Paper›PMID 29642281›Full record

ArticleImmunity, inflammation and disease2018

Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse.

Jeansun Lee, Nele M G Dieckmann, James R Edgar, Gillian M Griffiths, Richard M Siegel

Open access · goldAbstract read
In one paragraph

Article in Immunity, inflammation and disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Lysosome-related organelles orchestrate guanine crystal formation in pigment cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025
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  10. The Expanding Arsenal of Cytotoxic T Cells.Frontiers in immunology · 2022
    Review
  11. Review
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  13. Review
  14. ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Global gene expression profiling of blast lung injury of goats exposed to shock wave.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2020
    Article
  17. Review
  18. An early history of T cell-mediated cytotoxicity.Nature reviews. Immunology · 2018
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 4 countries.

Jeansun LeeCIMR, Department of Medicine, Cambridge University, Cambridge, UK.
Nele M G DieckmannCIMR, Department of Medicine, Cambridge University, Cambridge, UK.
James R EdgarCIMR, Department of Medicine, Cambridge University, Cambridge, UK.
Gillian M GriffithsCIMR, Department of Medicine, Cambridge University, Cambridge, UK.
Richard M SiegelImmunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-5953-9893
University of Cambridge · GBNational Institutes of Health · US

Funding

NIAMS Light Imaging FacilityZICAR041186 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI RANDAZZO, DAVIDE · 2010 to 2025
$18.2M
TNF-receptors and programmed cell death in regulation of autoimmunityZIAAR041133 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SIEGEL, RICHARD M · 2009 to 2019
$9.3M
Wellcome TrustWellcome Trust 103930
6 · The paper itself

Abstract

introductionT cell and NK cell cytotoxicity can be mediated via the perforin/granzyme system and Fas Ligand (FasL, CD178). FasL is synthesized as a type II transmembrane protein that binds its cognate receptor Fas (CD95). Membrane-bound FasL is expressed on the plasma membrane of activated lymphocytes and is the main form of FasL with cytotoxic activity, but whether FasL is delivered to the immune synapse along with granzyme and perforin-containing granules is unclear.

methodsWe stably expressed FasL-fluorescent fusion proteins into human NK cells and examined the localization of FasL relative to other intracellular markers by confocal and immunoelectron microscopy, and examined the trafficking of FasL during formation of immune synapses with HLA-deficient B cells.

resultsFasL co-localized with CD63 more strongly than perforin or Lamp1+ in cytolytic granules. Electron microscopy revealed that FasL is enriched on intraluminal vesicles (ILVs) adjacent to the dense-core within cytolytic granules. In NK cells forming immune synapses with HLA-deficient B cells, a portion of FasL-containing granules re-localize toward the immune synapse, while a distinct pool of FasL remains at the distal pole of the cell.

conclusionsLocalization of FasL to intra-luminal vesicles within cytolytic granules facilitates FasL trafficking to immune synapses and cytotoxic function in NK cells.

Indexed as

B-LymphocytesCell Culture TechniquesCell LineCytoplasmic GranulesFas Ligand ProteinGranzymesHLA AntigensHumansImmunological SynapsesKiller Cells, NaturalMicroscopy, ElectronPerforinTetraspanin 30CD63 protein, humanFASLG protein, humanFas Ligand ProteinGranzymesHLA AntigensPerforinPRF1 protein, humanTetraspanin 30Cytolytic granulesfas ligand (CD178)immune synapseintra-luminal vesicles (ILVs)

Identifiers

PMID29642281
PMCPMC5946154
OpenAlexW2805264087

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.