气候变化领域集成服务门户(CCPortal): Profound Treg perturbations correlate with COVID-19 severity

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DOI	10.1073/pnas.2111315118
	Profound Treg perturbations correlate with COVID-19 severity
	Galván-Peña S.; Leon J.; Chowdhary K.; Michelson D.A.; Vijaykumar B.; Yang L.; Magnuson A.M.; Chen F.; Manickas-Hill Z.; Piechocka-Trocha A.; Worrall D.P.; Hall K.E.; Ghebremichael M.; Walker B.D.; Li J.Z.; Yu X.G.; Mathis D.; Benoist C.; MGH COVID-19 Collection & Processing Team
发表日期	2021
ISSN	0027-8424
卷号	118 期号:37
英文摘要	The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19–linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	COVID-19; FoxP3; Tregs; Tumor Tregs
语种	英语
scopus关键词	C reactive protein; CD70 antigen; chemokine receptor CXCR3; interleukin 10; interleukin 12 receptor beta1; interleukin 18; interleukin 1beta; interleukin 32; interleukin 6; transcription factor FOXP3; transcription factor T bet; forkhead transcription factor; FOXP3 protein, human; IL18 protein, human; IL2RA protein, human; IL6 protein, human; interleukin 18; interleukin 2 receptor alpha; interleukin 6; transcription factor; adult; Article; CD4+ T lymphocyte; cohort analysis; controlled study; convalescence; coronavirus disease 2019; correlation analysis; disease severity; flow cytometry; gene overexpression; genetic transcription; human; human cell; major clinical study; protein expression; regulatory T lymphocyte; RNA sequencing; transcriptomics; aged; etiology; female; gene expression profiling; gene expression regulation; genetics; immunology; inflammation; male; metabolism; middle aged; physiology; regulatory T lymphocyte; severity of illness index; tumor associated leukocyte; virology; Adult; Aged; CD4-Positive T-Lymphocytes; COVID-19; Female; Forkhead Transcription Factors; Gene Expression Profiling; Gene Expression Regulation; Humans; Inflammation; Interleukin-18; Interleukin-2 Receptor alpha Subunit; Interleukin-6; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Severity of Illness Index; T-Lymphocytes, Regulatory; Transcription Factors
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/251022
作者单位	Department of Immunology, Harvard Medical School, Boston, MA 02115, United States; Imagine Institute, INSERM UMR 1163, University of Paris, Paris, 75015, France; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, United States; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, United States; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States; HHMI, Center for the AIDS Programme of Research in South Africa, Chevy Chase, MD 20815, United States; Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Galván-Peña S.,Leon J.,Chowdhary K.,et al. Profound Treg perturbations correlate with COVID-19 severity[J],2021,118(37).
APA	Galván-Peña S..,Leon J..,Chowdhary K..,Michelson D.A..,Vijaykumar B..,...&MGH COVID-19 Collection & Processing Team.(2021).Profound Treg perturbations correlate with COVID-19 severity.Proceedings of the National Academy of Sciences of the United States of America,118(37).
MLA	Galván-Peña S.,et al."Profound Treg perturbations correlate with COVID-19 severity".Proceedings of the National Academy of Sciences of the United States of America 118.37(2021).