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Cited by 82Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyDrug Transport and Resistance Mechanisms

The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells

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Castella, Barbara, Kopecka, Joanna, Sciancalepore, Patrizia, Mandili, Giorgia, Foglietta, Myriam, Mitro, Nico, Caruso, Donatella, Novelli, Francesco +2 more·2017·Nature Communications
DOI 10.1038/ncomms15663PMC PMC5465356
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Abstract

Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXRα nuclear translocation and PI3K/Akt/mTOR pathway inhibition. These results close the mechanistic gap in our understanding of extracellular IPP release from DC and provide a framework to fine-tune Vγ9Vδ2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation.

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  • Dendritic cells treated with a statin (zoledronic acid) increased ABCA1 which enhanced extracellular release of the phospho-antigen isopentenyl pyrophosphate, ultimately activating Vγ9Vδ2 T cells.

    “Using a somewhat contrived system, dendritic cells treated with a statin (zoledronic acid) increased ABCA1 which enhanced extracellular release of the phospho-antigen isopentenyl pyrophosphate, ultimately activating Vγ9Vδ2 T cells (72).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [72]

    The Results section (“ZA increases IPP efflux via LXRα-mediated Abca1 activation”) and Discussion support the chain from zoledronic acid (ZA) treatment to increased ABCA1, extracellular IPP release, and Vγ9Vδ2 T-cell activation. But the claim incorrectly calls ZA a statin: the paper identifies simvastatin as the statin and reports that it reduces ABCA1 expression and extracellular IPP release. Page numbers are not provided in our copy. (LLM, conf=0.93)

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Cited by

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Authors
Castella, B., Kopecka, J., Sciancalepore, P., Mandili, G., Foglietta, M., Mitro, N., Caruso, D., Novelli, F., Riganti, C., & Massaia, M.
Affiliations
  • Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
  • University of Turin (IT)
  • University of Milan (IT)
Corresponding author
  • Riganti, Chiara
  • Massaia, Massimo
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-06-05
Volume
8
Issue
1
Pages
15663-15663
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms15663
PMC
PMC5465356
OpenAlex
W2623744214
Cited by
82
References
0
Citations by year
2026: 8 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 13 · 2019: 2 · 2018: 14 · 2017: 3
FWCI
3.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Funders
  • Compagnia di San Paolo
  • Fondazione Umberto Veronesi (12182, 15257)
  • Associazione Italiana per la Ricerca sul Cancro (n. 12182, 12182, IG 15232, 16985, 5 x mille, 15257)
  • Università degli Studi di Torino
  • Fondazione Ricerca Molinette
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
ABCA1, isopentenyl pyrophosphate, Vγ9Vδ2 T cells, dendritic cells, mevalonate pathway, apolipoprotein A-I, zoledronic acid, PI3K/AKT/mTOR pathway, T cell activation
MeSH terms
Butyrophilins, Zoledronic Acid, Adenosine Triphosphate, Dendritic Cells, Humans, Lymphocyte Activation, Organophosphorus Compounds, Protein Binding, T-Lymphocytes, Antigens, CD, Immunophenotyping, Apolipoprotein A-I, Receptors, Antigen, T-Cell, gamma-delta, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Phosphatidylinositol 3-Kinases, U937 Cells, Active Transport, Cell Nucleus, Hemiterpenes, Cell Proliferation, Lipid Metabolism, ATP Binding Cassette Transporter 1

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