气候变化领域集成服务门户(CCPortal): TFH cells depend on Tcf1-intrinsic HDAC activity to suppress CTLA4 and guard B-cell help function

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DOI	10.1073/pnas.2014562118
	TFH cells depend on Tcf1-intrinsic HDAC activity to suppress CTLA4 and guard B-cell help function
	Li F.; Zhao X.; Zhang Y.; Shao P.; Ma X.; Paradee W.J.; Liu C.; Wang J.; Xue H.-H.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Precise regulation of coinhibitory receptors is essential for maintaining immune tolerance without interfering with protective immunity, yet the mechanism underlying such a balanced act remains poorly understood. In response to protein immunization, T follicular helper (TFH) cells lacking Tcf1 and Lef1 transcription factors were phenotypically normal but failed to promote germinal center formation and antibody production. Transcriptomic profiling revealed that Tcf1/Lef1-deficient TFH cells aberrantly up-regulated CTLA4 and LAG3 expression, and treatment with antiCTLA4 alone or combined with anti-LAG3 substantially rectified B-cell help defects by Tcf1/Lef1-deficient TFH cells. Mechanistically, Tcf1 and Lef1 restrain chromatin accessibility at the Ctla4 and Lag3 loci. Groucho/Tle corepressors, which are known to cooperate with Tcf/Lef factors, were essential for TFH cell expansion but dispensable for repressing coinhibitory receptors. In contrast, mutating key amino acids in histone deacetylase (HDAC) domain in Tcf1 resulted in CTLA4 derepression in TFH cells. These findings demonstrate that Tcf1-instrinsic HDAC activity is necessary for preventing excessive CTLA4 induction in protein immunization-elicited TFH cells and hence guarding their B-cell help function. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Coinhibitory pathway; Follicular helper T cells; Transcriptional regulation
语种	英语
scopus关键词	cytotoxic T lymphocyte antigen 4; histone deacetylase; lymphoid enhancer factor 1; transcription factor; transcription factor 7; transcription factor LAG3; unclassified drug; animal cell; antibody production; Article; B lymphocyte; CD4+ T lymphocyte; cell expansion; chromatin; complex formation; controlled study; enzyme activity; gene locus; germinal center; immune response; immunization; immunofluorescence; immunological tolerance; lymphocyte differentiation; lymphocyte function; mouse; mutation; nonhuman; phenotype; priority journal; protein expression; signal transduction; Tfh cell; transcription regulation; transcriptomics; upregulation
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/181041
作者单位	Department of Rheumatology and Immunology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China; Hefei National Laboratory for Physical Sciences at Microscale, Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China; Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ 07110, United States; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States; Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States; School of Computer Science and Technology, Xidian University, Xi'an, Shanxi, 215123, China; Genome Editing Core Facility, University of Iowa, Coralville, IA 52241, Uni...
推荐引用方式 GB/T 7714	Li F.,Zhao X.,Zhang Y.,et al. TFH cells depend on Tcf1-intrinsic HDAC activity to suppress CTLA4 and guard B-cell help function[J],2021,118(2).
APA	Li F..,Zhao X..,Zhang Y..,Shao P..,Ma X..,...&Xue H.-H..(2021).TFH cells depend on Tcf1-intrinsic HDAC activity to suppress CTLA4 and guard B-cell help function.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Li F.,et al."TFH cells depend on Tcf1-intrinsic HDAC activity to suppress CTLA4 and guard B-cell help function".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).