EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.

Autor:	Randzavola LO; Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom., Mortimer PM; Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom., Garside E; Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom., Dufficy ER; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom., Schejtman A; Molecular Immunology Unit, UCL Great Ormond Street Institute of Child Health, London, United Kingdom., Roumelioti G; Functional Proteomics, Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom., Yu L; Functional Proteomics, Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom., Pardo M; Functional Proteomics, Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom., Spirohn K; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, United States.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, United States., Tolley C; Wellcome Trust Sanger Institute, Hinxton, United Kingdom., Brandt C; Wellcome Trust Sanger Institute, Hinxton, United Kingdom., Harcourt K; Wellcome Trust Sanger Institute, Hinxton, United Kingdom., Nichols E; Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom., Nahorski M; Cambridge Institute of Medical Research, University of Cambridge, Cambridge, United Kingdom., Woods G; Cambridge Institute of Medical Research, University of Cambridge, Cambridge, United Kingdom., Williamson JC; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.; Cambridge Institute of Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, United Kingdom., Suresh S; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom., Sowerby JM; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.; Cambridge Institute of Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, United Kingdom., Matsumoto M; Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Japan., Santos CXC; School of Cardiovascular Medicine and Sciences, James Black Centre, King's College London, London, United Kingdom., Kiar CS; Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom., Mukhopadhyay S; Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom., Rae WM; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.; Cambridge Institute of Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, United Kingdom., Dougan GJ; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom., Grainger J; Functional Proteomics, Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom.; Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Lehner PJ; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.; Cambridge Institute of Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, United Kingdom., Calderwood MA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, United States.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, United States., Choudhary J; Functional Proteomics, Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom., Clare S; Wellcome Trust Sanger Institute, Hinxton, United Kingdom., Speak A; Wellcome Trust Sanger Institute, Hinxton, United Kingdom., Santilli G; Molecular Immunology Unit, UCL Great Ormond Street Institute of Child Health, London, United Kingdom., Bateman A; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom., Smith KGC; The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.; Cambridge Institute of Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, United Kingdom., Magnani F; Department of Biology and Biotechnology, University of Pavia, Pavia, Italy., Thomas DC; Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Nov 24; Vol. 11. Date of Electronic Publication: 2022 Nov 24.
DOI:	10.7554/eLife.76387
Abstrakt:	EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91 phox , the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91 phox maturation. It binds the immature 58 kDa gp91 phox directly, preventing gp91 phox degradation and allowing glycosylation via the oligosaccharyltransferase machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions, and P2X7 is almost absent in EROS-deficient mouse and human primary cells. Accordingly, lack of murine EROS results in markedly abnormal P2X7 signalling, inflammasome activation, and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection in mice. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation, and possibly gene therapy. Competing Interests: LR, PM, EG, ED, AS, GR, LY, MP, KS, CT, CB, KH, EN, MN, GW, JW, SS, JS, MM, CS, CK, SM, WR, GD, JG, PL, MC, JC, SC, AS, GS, AB, KS, FM, DT No competing interests declared (© 2022, Randzavola, Mortimer et al.)
Databáze:	MEDLINE
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