Evidence map›Paper›PMID 39704712›Full record

ArticleThe Journal of experimental medicine2025

Identification of α-galactosylceramide as an endogenous mammalian antigen for iNKT cells.

Yuki Hosono, Noriyuki Tomiyasu, Hayato Kasai, Eri Ishikawa, Masatomo Takahashi, Akihiro Imamura, Hideharu Ishida, Federica Compostella, Hiroshi Kida, Atsushi Kumanogoh and 3 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. 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

13 authors.

Yuki Hosono *Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.ORCID 0000-0001-9993-6789
Noriyuki Tomiyasu *Department of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.ORCID 0000-0003-4619-2805
Hayato Kasai *Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.ORCID 0009-0002-3316-0425
Eri IshikawaDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.ORCID 0000-0002-4922-6751
Masatomo TakahashiDepartment of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.ORCID 0000-0002-2493-2684
Akihiro ImamuraDepartment of Applied Bioorganic Chemistry, Gifu University, Gifu, Japan.ORCID 0000-0002-7860-992X
Hideharu IshidaDepartment of Applied Bioorganic Chemistry, Gifu University, Gifu, Japan.ORCID 0000-0002-8625-0929
Federica CompostellaDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.ORCID 0000-0003-4721-0358
Hiroshi KidaDepartment of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan.ORCID 0000-0002-9351-7855
Atsushi KumanogohDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.ORCID 0000-0003-4749-7117
Takeshi BambaDepartment of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.ORCID 0000-0002-7442-2738
Yoshihiro IzumiDepartment of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.ORCID 0000-0003-4608-4652
Sho YamasakiDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.ORCID 0000-0002-5184-6917

Funding

Japan Agency for Medical Research and Development JP23wm0325054Japan Society for the Promotion of Science JP22J11145Ministry of Education, Culture, Sports, Science and Technology JP22H05183Osaka University
6 · The paper itself

Abstract

Invariant natural killer T (iNKT) cells are unconventional T cells recognizing lipid antigens in a CD1d-restricted manner. Among these lipid antigens, α-galactosylceramide (α-GalCer), which was originally identified in marine sponges, is the most potent antigen. Although the presence of α-anomeric hexosylceramide and microbiota-derived branched α-GalCer is reported, antigenic α-GalCer has not been identified in mammals. Here, we developed a high-resolution separation and detection system, supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS), that can discriminate hexosylceramide diastereomers (α-GalCer, α-GlcCer, β-GalCer, or β-GlcCer). The B16 melanoma tumor cell line does not activate iNKT cells; however, ectopic expression of CD1d was sufficient to activate iNKT cells without adding antigens. B16 melanoma was unlikely to generate iNKT cell antigens; instead, antigen activity was detected in cell culture serum. Activity-based purification and SFC/MS/MS identified dihydrosphingosine-based saturated α-GalCer as an antigenic component in serum, bile, and lymphoid tissues. These results show the first evidence for the presence of potent antigenic α-GalCer in mammals.

Indexed as

Antigens, CD1dGalactosylceramidesMelanoma, ExperimentalMice, Inbred C57BLNatural Killer T-CellsAnimalsAntigensCell Line, TumorLymphocyte ActivationMiceTandem Mass Spectrometryalpha-galactosylceramideAntigensAntigens, CD1dGalactosylceramides

Identifiers

PMID39704712
PMCPMC11660903

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Registered trials

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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.