Evidence map›Paper›PMID 35210420›Full record

ArticleNature communications2022

Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes.

Hsin-Fang Chang, Claudia Schirra, Momchil Ninov, Ulrike Hahn, Keerthana Ravichandran, Elmar Krause, Ute Becherer, Štefan Bálint, Maria Harkiolaki, Henning Urlaub and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 64 citations in OpenAlex.

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  12. Activation-induced thrombospondin-4 works with thrombospondin-1 to build cytotoxic supramolecular attack particles.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Harnessing extracellular vesicle-mediated crosstalk between T cells and cancer cells for therapeutic applications.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Review
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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

15 authors at 6 institutions in 4 countries.

Hsin-Fang Chang *Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany. Hsin-Fang.Chang@uks.eu.ORCID http://orcid.org/0000-0002-7691-4090
Claudia Schirra *Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.
Momchil NinovBioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077, Göttingen, Germany.ORCID http://orcid.org/0000-0002-0808-7003
Ulrike HahnCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.
Keerthana RavichandranCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.
Elmar KrauseCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0003-0891-2373
Ute BechererCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0001-6005-7517
Štefan BálintKennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7FY, Oxford, UK.ORCID http://orcid.org/0000-0003-4470-5881
Maria HarkiolakiDiamond Light Source, Harwell Science and Innovation Campus, OX11 0DE, Didcot, UK.ORCID http://orcid.org/0000-0001-8091-9057
Henning UrlaubBioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077, Göttingen, Germany.ORCID http://orcid.org/0000-0003-1837-5233
Salvatore ValituttiCancer Research Center of Toulouse, INSERM U1037, 31037, Toulouse, France.ORCID http://orcid.org/0000-0002-6432-4421
Cosima T BaldariDepartment of Life Sciences, University of Siena, 53100, Siena, Italy.
Michael L DustinKennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7FY, Oxford, UK.ORCID http://orcid.org/0000-0003-4983-6389
Reinhard JahnLaboratory of Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077, Göttingen, Germany.ORCID http://orcid.org/0000-0003-1542-3498
Jens RettigCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany. jrettig@uks.eu.
Saarland University · DEMax Planck Institute for Multidisciplinary SciencesUniversity of Oxford · GBDiamond Light Source · GBInserm · FRUniversity of Siena · IT

Funding

European Research Council 951329Wellcome Trust
6 · The paper itself

Abstract

Cytotoxic T lymphocytes (CTL) kill malignant and infected cells through the directed release of cytotoxic proteins into the immunological synapse (IS). The cytotoxic protein granzyme B (GzmB) is released in its soluble form or in supramolecular attack particles (SMAP). We utilize synaptobrevin2-mRFP knock-in mice to isolate fusogenic cytotoxic granules in an unbiased manner and visualize them alone or in degranulating CTLs. We identified two classes of fusion-competent granules, single core granules (SCG) and multi core granules (MCG), with different diameter, morphology and protein composition. Functional analyses demonstrate that both classes of granules fuse with the plasma membrane at the IS. SCG fusion releases soluble GzmB. MCGs can be labelled with the SMAP marker thrombospondin-1 and their fusion releases intact SMAPs. We propose that CTLs use SCG fusion to fill the synaptic cleft with active cytotoxic proteins instantly and parallel MCG fusion to deliver latent SMAPs for delayed killing of refractory targets.

Indexed as

Immunological SynapsesT-Lymphocytes, CytotoxicAnimalsCell MembraneCytoplasmic GranulesMice

Identifiers

PMID35210420
PMCPMC8873490
OpenAlexW4213415790

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.