NLRC5 promotes transcription of BTN3A1-3 genes and Vγ9Vδ2 T cell-mediated killing.

Autor:	Dang AT; Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland., Strietz J; Department of Immunology, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany., Zenobi A; Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland., Khameneh HJ; Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland., Brandl SM; Department of Immunology, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany., Lozza L; Department of Immunology, Max Planck Institute for Infection Biology, Berlin 10117, Germany., Conradt G; Department of Immunology, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany., Kaufmann SHE; Department of Immunology, Max Planck Institute for Infection Biology, Berlin 10117, Germany.; Hagler Institute for Advanced Study at Texas A&M University, College Station, TX 77843, USA., Reith W; Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland., Kwee I; Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland., Minguet S; Department of Immunology, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Chelbi ST; Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland., Guarda G; Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2020 Dec 07; Vol. 24 (1), pp. 101900. Date of Electronic Publication: 2020 Dec 07 (Print Publication: 2021).
DOI:	10.1016/j.isci.2020.101900
Abstrakt:	BTN3A molecules-BTN3A1 in particular-emerged as important mediators of Vγ9Vδ2 T cell activation by phosphoantigens. These metabolites can originate from infections, e.g. with Mycobacterium tuberculosis, or by alterations in cellular metabolism. Despite the growing interest in the BTN3A genes 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 between NLRC5 and BTN3A gene expression was found in healthy, in M. 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 of BTN3A genes and hence open opportunities to modulate antimicrobial and anticancer immunity. Competing Interests: Other projects in G.G. laboratory are supported by OM-Pharma, Meyrin, IFM Therapeutics, Boston, and Novartis Foundation. Unrelated projects in SM laboratory are supported by the Eurostars program (EUROPEAN UNION HORIZON, 2020 FRAMEWORK PROGRAM). (© 2020 The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu