Evidence map›Paper›PMID 40389449›Full record

ArticleCell death & disease2025

IFT20 regulates TFEB-dependent lytic granule biogenesis in cytotoxic T lymphocytes by orchestrating the MPR-dependent transport of granzyme B.

Francesca Finetti, Fabrizia Zevolini, Loredana Migliore, Valentina Cianfanelli, Leandro Marzuoli, Nagaja Capitani, Chiara Cassioli, Laura Patrussi, Cristina Ulivieri, Giuseppe Marotta and 1 more

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Francesca Finetti *Department of Life Sciences, University of Siena, Siena, Italy. finetti4@unisi.it.ORCID http://orcid.org/0000-0002-3421-1637
Fabrizia Zevolini *Department of Life Sciences, University of Siena, Siena, Italy.
Loredana MiglioreDepartment of Life Sciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0003-0395-1496
Valentina CianfanelliDepartment of Science, University "ROMA TRE", Rome, Italy.ORCID http://orcid.org/0000-0002-3857-9463
Leandro MarzuoliDepartment of Life Sciences, University of Siena, Siena, Italy.
Nagaja CapitaniDepartment of Life Sciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0003-3653-8972
Chiara CassioliDepartment of Life Sciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-4853-2298
Laura PatrussiDepartment of Life Sciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0003-1542-6955
Cristina UlivieriDepartment of Life Sciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-1710-7977
Giuseppe MarottaSiena University Hospital, Siena, Italy.
Cosima T BaldariDepartment of Life Sciences, University of Siena, Siena, Italy. cosima.baldari@unisi.it.ORCID http://orcid.org/0000-0002-4414-6744

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) IG 2017-20148European Commission (EC) ERC_2021_SyG 951329 - ATTACKMinistero della Salute (Ministry of Health, Italy) GR-2021-12372771Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) PRIN 2022 Bando PNRR P2022TJZYZ
6 · The paper itself

Abstract

Cytotoxic T lymphocytes (CTL) exploit specialized secretory lysosomes, the lytic granules (LG) to kill target cells. The LGs carry a battery of apoptosis-inducing molecules enriched in granzymes (GZM), perforin and FasL, which are released at the immune synapse formed by CTLs with their cognate targets. Recent studies have revealed an unexpected diversity among LGs, suggesting the existence of multiple vesicular trafficking pathways in their biogenesis and exocytosis. We have previously implicated the ciliary protein IFT20 in the retrograde trafficking of the cation-independent mannose-6-phosphate receptor (MPR), which is required for the lysosomal targeting of the acid hydrolases. Here we investigate the role of IFT20 in LG biogenesis in CTLs, showing that IFT20 is essential for MPR recycling to the trans-Golgi network and ensures proper granzyme B (GZMB) localization to LGs. As a result, IFT20 deficiency impairs the killing capability of CTLs. In turn, to rescue the lysosome and LG defects, IFT20-deficient CTLs expresses higher levels of lysosomal genes and of components of the cytotoxic machinery of LGs. Interestingly, an in silico analysis suggests a transcriptional co-regulation of lysosome and LG genes by the master regulator of lysosome biogenesis TFEB. Accordingly, modulation of TFEB results in alterations in the expression of LG-related genes and CTL-mediated cytotoxicity. Collectively, our results identify IFT20 as a new player in the trafficking pathways that regulate LG biogenesis and highlight the existence in CTLs of an extended gene expression program regulated by TFEB, downstream of IFT20.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarrier ProteinsCytoplasmic GranulesGranzymesReceptor, IGF Type 2T-Lymphocytes, CytotoxicAnimalsHumansLysosomesMiceProtein Transporttrans-Golgi NetworkBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarrier ProteinsGranzymesReceptor, IGF Type 2TFEB protein, human

Identifiers

PMID40389449
PMCPMC12089405

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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.