摘要：SummaryBTN3A molecules—BTN3A1 in particular—emerged as important mediators of Vγ9Vδ2 T cell activation by phosphoantigens. These metabolites can originate from infections, e.g. withMycobacterium tuberculosis,or by alterations in cellular metabolism. Despite the growing interest in theBTN3Agenes and their high expression in immune cells and various cancers, little is known about their transcriptional regulation. Here we show that these genes are induced by NLRC5, a regulator of MHC class I gene transcription, through an atypical regulatory motif found in their promoters. Accordingly, a robust correlation betweenNLRC5andBTN3Agene expression was found in healthy, inM. tuberculosis-infected donors' blood cells, and in primary tumors. Moreover, forcing NLRC5 expression promoted Vγ9Vδ2 T-cell-mediated killing of tumor cells in a BTN3A-dependent manner. Altogether, these findings indicate that NLRC5 regulates the expression ofBTN3Agenes and hence open opportunities to modulate antimicrobial and anticancer immunity.Graphical AbstractDisplay OmittedHighlights•BTN3Apromoters contain a unique regulatory motif occupied by overexpressed NLRC5•NLRC5andBTN3AmRNA levels correlate in healthy and diseased cells•NLRC5 overexpression increases susceptibility to Vγ9Vδ2 T-cell-mediated eliminationImmunology; Microbiology; Cell Biology
