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

被引：62

作者：

Castella, Barbara ^{[1
,2
]}

Kopecka, Joanna ^{[3
]}

Sciancalepore, Patrizia ^{[1
,2
]}

Mandili, Giorgia ^{[1
,4
]}

Foglietta, Myriam ^{[1
,2
]}

Mitro, Nico ^{[5
]}

Caruso, Donatella ^{[5
]}

Novelli, Francesco ^{[1
,4
]}

Riganti, Chiara ^{[2
,3
]}

Massaia, Massimo ^{[1
,2
,4
,6
]}

机构：

[1] Univ Turin, Dipartimento Biotecnol Mol & Sci Salute, Via Nizza 52, I-10126 Turin, Italy

[2] AOU Citta Salute & Sci Torino, Ctr Ric Med Sperimentale CeRMS, Via Santena 5, I-10126 Turin, Italy

[3] Univ Turin, Dipartimento Oncol, Via Santena 5 Bis, I-10126 Turin, Italy

[4] CIRBM, Via Nizza 52, I-10126 Turin, Italy

[5] Univ Milan, Dipartimento Sci Farmacol & Biomol, Via Balzaretti 9, I-20133 Milan, Italy

[6] AO S Croce & Carle, SC Ematol, Via Michele Coppino 26, I-12100 Cuneo, Italy

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

COLON-CANCER CELLS; BUTYROPHILIN; 3A1; ZOLEDRONIC ACID; X RECEPTOR; PHOSPHORYLATED ANTIGENS; P-GLYCOPROTEIN; MODULATION; INHIBITION; STRESS; STIMULATION;

D O I：

10.1038/ncomms15663

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

V gamma 9V delta 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 V gamma 9V delta 2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXR alpha 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 V gamma 9V delta 2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation.

引用

页数：14

共 55 条

[21] Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset [J].