气候变化领域集成服务门户(CCPortal): UFMylation inhibits the proinflammatory capacity of interferon-γ

CCPortal

DOI	10.1073/PNAS.2011763118
	UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages
	Balce D.R.; Wang Y.-T.; McAllaster M.R.; Dunlap B.F.; Orvedahl A.; Hykes B.L.; Droit L.; Handley S.A.; Wilen C.B.; Doench J.G.; Orchard R.C.; Stallings C.L.; Virgin H.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:1
英文摘要	Macrophages activated with interferon-γ (IFN-γ) in combination with other proinflammatory stimuli, such as lipopolysaccharide or tumor necrosis factor-α (TNF-α), respond with transcriptional and cellular changes that enhance clearance of intracellular pathogens at the risk of damaging tissues. IFN-γ effects must therefore be carefully balanced with inhibitory mechanisms to prevent immunopathology. We performed a genome-wide CRISPR knockout screen in a macrophage cell line to identify negative regulators of IFN-γ responses. We discovered an unexpected role of the ubiquitin-fold modifier (Ufm1) conjugation system (herein UFMylation) in inhibiting responses to IFN-γ and lipopolysaccharide. Enhanced IFN-γ activation in UFMylation-deficient cells resulted in increased transcriptional responses to IFN-γ in a manner dependent on endoplasmic reticulum stress responses involving Ern1 and Xbp1. Furthermore, UFMylation in myeloid cells is required for resistance to influenza infection in mice, indicating that this pathway modulates in vivo responses to infection. These findings provide a genetic roadmap for the regulation of responses to a key mediator of cellular immunity and identify a molecular link between the UFMylation pathway and immune responses. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autophagy; ER stress; Immunology; Interferon; UFMylation
语种	英语
scopus关键词	gamma interferon; animal experiment; animal model; animal tissue; Article; autophagy (cellular); bone marrow cell; clustered regularly interspaced short palindromic repeat; controlled study; cytokine response; endoplasmic reticulum stress; genome-wide association study; immune response; macrophage activation; mouse; nonhuman; priority journal; ubiquitination
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/181120
作者单位	Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States; Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06510, United States; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, United States; Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States; Department of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
推荐引用方式 GB/T 7714	Balce D.R.,Wang Y.-T.,McAllaster M.R.,等. UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages[J],2021,118(1).
APA	Balce D.R..,Wang Y.-T..,McAllaster M.R..,Dunlap B.F..,Orvedahl A..,...&Virgin H.W..(2021).UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages.Proceedings of the National Academy of Sciences of the United States of America,118(1).
MLA	Balce D.R.,et al."UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021).