Evidence map›Paper›PMID 42550837›Full record

ArticlePloS one2026

Tyro3 facilitates cytoplasmic delivery of extracellular vesicle contents and antigen presentation via major histocompatibility complex class I in dendritic cells.

Takashi Koyama, Katsuhiko Kojima, Koki Maeda, Takahide Matsui, Hitomi Kosai, Noriko Ishida, Eiji Morita, Mitsunori Fukuda, Nobuyuki Tanaka

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Takashi KoyamaDivision of Tumor Immunobiology, Miyagi Cancer Center Research Institute, Natori, Japan.ORCID https://orcid.org/0009-0005-6322-724X
Katsuhiko KojimaDepartment of Immunology and Microbiology, Shinshu University School of Medicine, Matsumoto, Japan.
Koki MaedaDepartment of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan.
Takahide MatsuiLaboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
Hitomi KosaiDivision of Tumor Immunobiology, Miyagi Cancer Center Research Institute, Natori, Japan.
Noriko IshidaDivision of Tumor Immunobiology, Miyagi Cancer Center Research Institute, Natori, Japan.
Eiji MoritaDepartment of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan.
Mitsunori FukudaLaboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
Nobuyuki TanakaDivision of Tumor Immunobiology, Miyagi Cancer Center Research Institute, Natori, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Extracellular vesicles (EVs) are membrane-bound particles that mediate intercellular communication and are being explored as carriers for antigen delivery in cancer immunotherapy. However, the molecular mechanisms underlying the uptake of antigen-carrying EVs by dendritic cells (DCs) remain unclear. EV uptake is influenced by the recognition of EV surface components by receptors on recipient cells. Phospholipids, including phosphatidylserine (PS), are common structural components of EV membrane. We therefore focused on the TAM receptor tyrosine kinases Tyro3, Axl, and Mertk, which are expressed in antigen-presenting cells and engage PS-exposing membranes through the bridging ligands Growth arrest-specific 6 (Gas6) and Protein S (Pros1). Using the DC2.4 dendritic cell line as a model system, we investigated the involvement of TAM receptors in the uptake of small EVs (sEVs) and subsequent antigen presentation. We found that Tyro3 binding to sEVs was enhanced by Gas6 and Pros1, and that Tyro3 also associated with phosphatidylserine (PS) and phosphatidylglycerol (PG) through these bridging ligands. Among TAM receptors, only Tyro3 markedly enhanced sEV internalization in DC2.4 cells. Deletion analysis indicated that the immunoglobulin C2-type domain (IG2c domain) of Tyro3 is required for efficient sEV association and uptake. Moreover, Tyro3-mediated internalization enabled cross-presentation of sEV-delivered antigens and activation of CD8+ T cells. This function required a 46-amino acid intracellular region of Tyro3, which we designated the Tyro3 antigen presentation-related domain (TAPD); deletion of TAPD impaired cross-presentation of sEV-delivered antigens. Finally, we observed an increase in the frequency of Tyro3 ⁺ DCs in the spleens of tumor-bearing mice. These findings suggest that Tyro3 mediates sEV uptake and antigen cross-presentation in DCs and may represent a candidate molecular target for EV-based cancer immunotherapy.

Indexed as

Antigen PresentationCytoplasmDendritic CellsExtracellular VesiclesHistocompatibility Antigens Class IReceptor Protein-Tyrosine KinasesAnimalsCell Linec-Mer Tyrosine KinaseGrowth Arrest-Specific Protein 6Intercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLProtein Sc-Mer Tyrosine KinaseGrowth Arrest-Specific Protein 6Histocompatibility Antigens Class IIntercellular Signaling Peptides and ProteinsProtein SReceptor Protein-Tyrosine KinasesTyro3 protein, mouse

Identifiers

PMID42550837
PMCPMC13436743

What Socratic holds

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LicenceCC BY
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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 Socratic graph.