VÎ³39VÎ´2 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 VÎ³39VÎ´2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXRÎ± 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 VÎ³39VÎ´2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation.
|Titolo:||The ATP-binding cassette transporter A1 regulates phosphoantigen release and VÎ³39VÎ´2 T cell activation by dendritic cells|
MITRO, NICO [Membro del Collaboration Group]
|Parole Chiave:||chemistry (all); biochemistry, genetics and molecular biology (all); physics and astronomy (all)|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||5-giu-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/ncomms15663|
|Appare nelle tipologie:||01 - Articolo su periodico|