Evidence map›Paper›PMID 24248359›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation.

Mariolina Salio, Hemza Ghadbane, Omer Dushek, Dawn Shepherd, Jeremy Cypen, Uzi Gileadi, Michael C Aichinger, Giorgio Napolitani, Xiaoyang Qi, P Anton van der Merwe and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

27 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Observational
  7. Ligand-dependent downregulation of MR1 cell surface expression.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  8. 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 · 2019
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
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  16. Article
  17. Article
  18. Article
  19. From Lysosomal Storage Diseases to NKT Cell Activation and Back.International journal of molecular sciences · 2017
    Review
  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

17 authors at 7 institutions in 2 countries.

Mariolina SalioMedical Research Council Human Immunology Unit, Radcliffe Department of Medicine, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Hemza Ghadbane
Omer Dushek
Dawn Shepherd
Jeremy Cypen
Uzi Gileadi
Michael C Aichinger
Giorgio Napolitani
Xiaoyang Qi
P Anton van der Merwe
Justyna Wojno
Natacha Veerapen
Liam R Cox
Gurdyal S Besra
Weiming Yuan
Peter Cresswell
Vincenzo Cerundolo
Medical Research Council · GBUniversity of Birmingham · GBMRC Human Immunology Unit · GBUniversity of Oxford · GBCincinnati Children's Hospital Medical Center · USUniversity of Southern California · USYale University · US

Funding

Molecular Aspects of Human CD1d FunctionsR01AI059167 · NIAID · YALE UNIVERSITY · PI CRESSWELL, PETER · 2004 to 2019
$5.6M
Herpes simplex virus-1 evasion of CD1d antigen presentation pathwayR01AI091987 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YUAN, WEIMING · 2012 to 2016
$2.0M
Acidic Phospholipid-Selective Treatment for NeuroblastomaR01CA158372 · NCI · UNIVERSITY OF CINCINNATI · PI QI, XIAOYANG · 2011 to 2015
$1.6M
Cancer Research UK 11331Cancer Research UK C399/A2291Medical Research Council G1000800Medical Research Council G1001750Medical Research Council MC_UU_12010/1NCI NIH HHS R01 CA158372NIAID NIH HHS R01 AI059167NIAID NIH HHS R01 AI091987Wellcome Trust 084923/B/08/ZWellcome Trust 084923Z/08/ZWellcome Trust 098363
6 · The paper itself

Abstract

Lipid transfer proteins, such as molecules of the saposin family, facilitate extraction of lipids from biological membranes for their loading onto CD1d molecules. Although it has been shown that prosaposin-deficient mice fail to positively select invariant natural killer T (iNKT) cells, it remains unclear whether saposins can facilitate loading of endogenous iNKT cell agonists in the periphery during inflammatory responses. In addition, it is unclear whether saposins, in addition to loading, also promote dissociation of lipids bound to CD1d molecules. To address these questions, we used a combination of cellular assays and demonstrated that saposins influence CD1d-restricted presentation to human iNKT cells not only of exogenous lipids but also of endogenous ligands, such as the self-glycosphingolipid β-glucopyranosylceramide, up-regulated by antigen-presenting cells following bacterial infection. Furthermore, we demonstrated that in human myeloid cells CD1d-loading of endogenous lipids after bacterial infection, but not at steady state, requires trafficking of CD1d molecules through an endo-lysosomal compartment. Finally, using BIAcore assays we demonstrated that lipid-loaded saposin B increases the off-rate of lipids bound to CD1d molecules, providing important insights into the mechanisms by which it acts as a "lipid editor," capable of fine-tuning loading and unloading of CD1d molecules. These results have important implications in understanding how to optimize lipid-loading onto antigen-presenting cells, to better harness iNKT cells central role at the interface between innate and adaptive immunity.

Indexed as

Antigen-Presenting CellsAntigens, CD1dBacteriaEnzyme-Linked Immunosorbent AssayHEK293 CellsHumansImmunity, InnateImmunoprecipitationLipid MetabolismNatural Killer T-CellsSaposinsScintillation CountingAntigens, CD1dCD1D protein, humanSaposinsautoreactivityinflammationinnate immunitylipid binding proteins

Identifiers

PMID24248359
PMCPMC3856826
OpenAlexW2029933983

What OpenQuestion holds

Textmetadata
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.