气候变化领域集成服务门户(CCPortal): Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease

CCPortal

DOI	10.1073/pnas.2102804118
	Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease
	Le Voyer T.; Neehus A.-L.; Yang R.; Ogishi M.; Rosain J.; Alroqi F.; Alshalan M.; Blumental S.; Ali F.A.; Khan T.; Ata M.; Rozen L.; Demulder A.; Bastard P.; Gruber C.; Roynard M.; Seeleuthener Y.; Rapaport F.; Bigio B.; Chrabieh M.; Sng D.; Berteloot L.; Boddaert N.; Rozenberg F.; Al-Muhsen S.; Bertoli-Avella A.; Abel L.; Bogunovic D.; Marr N.; Mansouri D.; Mutairi F.A.; Béziat V.; Weil D.; Mahdaviani S.A.; Ferster A.; Zhang S.-Y.; Reversade B.; Boisson-Dupuis S.; Casanova J.-L.; Bustamante J.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient IFN-γ production by lymphoid cells, impaired myeloid cell responses to this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. The patients are homozygous for ZNFX1 variants (p.S959* and p.E1606Rfs10) predicted to be loss of function (pLOF). There are no subjects homozygous for pLOF variants in public databases. ZNFX1 is a conserved and broadly expressed helicase, but its biology remains largely unknown. It is thought to act as a viral double-stranded RNA sensor in mice, but these patients do not suffer from severe viral illnesses. We analyze its subcellular localization upon overexpression in A549 and HeLa cell lines and upon stimulation of THP1 and fibroblastic cell lines. We find that this cytoplasmic protein can be recruited to or even induce stress granules. The endogenous ZNFX1 protein in cell lines of the patient homozygous for the p.E1606Rfs10 variant is truncated, whereas ZNFX1 expression is abolished in cell lines from the patients with the p.S959* variant. Lymphocyte subsets are present at normal frequencies in these patients and produce IFN-γ normally. The hematopoietic and nonhematopoietic cells of the patients tested respond normally to IFN-γ. Our results indicate that human ZNFX1 is associated with stress granules and essential for both monocyte homeostasis and protective immunity to mycobacteria. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Inborn error of immunity; Inflammation; Monocytosis; Mycobacteria; ZNFX1
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179898
作者单位	Laboratory of Human Genetics of Infectious Diseases, INSERM, UMR 1163, Paris, 75015, France; Imagine Institute, University of Paris, Paris, 75015, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY 10065, United States; Immunology Division, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, 11426, Saudi Arabia; King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, 11426, Saudi Arabia; Genetics & Precision Medicine Department, King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Riyadh, 11426, Saudi Arabia; Paediatric Infectious Diseases Unit, Queen Fabiola Children's University Hospital, Brussels, 1020, Belgium; Research Branch, Sidra Medicine, Doha, Qatar; Laboratory of Hematology, LHUB-ULB, Free University of Brussels ULB, Brussels, 1020, Belgium; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United Sta...
推荐引用方式 GB/T 7714	Le Voyer T.,Neehus A.-L.,Yang R.,et al. Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease[J],2021,118(15).
APA	Le Voyer T..,Neehus A.-L..,Yang R..,Ogishi M..,Rosain J..,...&Bustamante J..(2021).Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Le Voyer T.,et al."Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).