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

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  • Barbara Castella

    (Università degli Studi di Torino
    Centro di Ricerca in Medicina Sperimentale (CeRMS), AOU Città della Salute e della Scienza di Torino)

  • Joanna Kopecka

    (Università degli Studi di Torino)

  • Patrizia Sciancalepore

    (Università degli Studi di Torino
    Centro di Ricerca in Medicina Sperimentale (CeRMS), AOU Città della Salute e della Scienza di Torino)

  • Giorgia Mandili

    (Università degli Studi di Torino
    Centro Interdipartimentale di Ricerca per le Biotecnologie Molecolari (CIRBM))

  • Myriam Foglietta

    (Università degli Studi di Torino
    Centro di Ricerca in Medicina Sperimentale (CeRMS), AOU Città della Salute e della Scienza di Torino)

  • Nico Mitro

    (Università degli Studi di Milano)

  • Donatella Caruso

    (Università degli Studi di Milano)

  • Francesco Novelli

    (Università degli Studi di Torino
    Centro Interdipartimentale di Ricerca per le Biotecnologie Molecolari (CIRBM))

  • Chiara Riganti

    (Centro di Ricerca in Medicina Sperimentale (CeRMS), AOU Città della Salute e della Scienza di Torino
    Università degli Studi di Torino)

  • Massimo Massaia

    (Università degli Studi di Torino
    Centro di Ricerca in Medicina Sperimentale (CeRMS), AOU Città della Salute e della Scienza di Torino
    Centro Interdipartimentale di Ricerca per le Biotecnologie Molecolari (CIRBM)
    SC. Ematologia, AO S. Croce e Carle)

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.

Suggested Citation

  • Barbara Castella & Joanna Kopecka & Patrizia Sciancalepore & Giorgia Mandili & Myriam Foglietta & Nico Mitro & Donatella Caruso & Francesco Novelli & Chiara Riganti & Massimo Massaia, 2017. "The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15663
    DOI: 10.1038/ncomms15663
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    Cited by:

    1. Nekisa Zakeri & Andrew Hall & Leo Swadling & Laura J. Pallett & Nathalie M. Schmidt & Mariana O. Diniz & Stephanie Kucykowicz & Oliver E. Amin & Amir Gander & Massimo Pinzani & Brian R. Davidson & Alb, 2022. "Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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