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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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The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells
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Journal Article
The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells
2017
Overview
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.
γδT cells are activated by phosphoantigens, and ABCA1 is involved in cholesterol transport. Here the authors link these ideas to show that ABCA1, apoA-I and BTN3A1 regulate extracellular phosphoantigen release by dendritic cells, and implicate ABCA1 in mevalonate-mediated activation of Vγ9Vδ2 T cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82
/ 82/1
/ 82/80
/ Active Transport, Cell Nucleus
/ Adenosine Triphosphate - chemistry
/ Apolipoprotein A-I - metabolism
/ ATP Binding Cassette Transporter 1 - metabolism
/ Dendritic Cells - immunology
/ Dendritic Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Lymphocyte Activation - immunology
/ Phosphatidylinositol 3-Kinases - metabolism
/ Receptors, Antigen, T-Cell, gamma-delta - immunology
/ Science
/ Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
