气候变化领域集成服务门户(CCPortal): DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions

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DOI	10.1073/pnas.2021309118
	DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions
	Sato K.; Yamashita-Kanemaru Y.; Abe F.; Murata R.; Nakamura-Shinya Y.; Kanemaru K.; Muratani M.; Veillette A.; Goto M.; Ito M.; Shibuya A.; Shibuya K.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:21
英文摘要	Regulatory T (Treg) cells that express forkhead box P3 (Foxp3) are pivotal for immune tolerance. Although inflammatory mediators cause Foxp3 instability and Treg cell dysfunction, their regulatory mechanisms remain incompletely understood. Here, we show that the transfer of Treg cells deficient in the activating immunoreceptor DNAM-1 ameliorated the development of graft-versus-host disease better than did wild-type Treg cells. We found that DNAM-1 competes with T cell immunoreceptor with Ig and ITIM domains (TIGIT) in binding to their common ligand CD155 and therefore regulates TIGIT signaling to down-regulate Treg cell function without DNAM-1–mediated intracellular signaling. DNAM-1 deficiency augments TIGIT signaling; this subsequently inhibits activation of the protein kinase B–mammalian target of rapamycin complex 1 pathway, resulting in the maintenance of Foxp3 expression and Treg cell function under inflammatory conditions. These findings demonstrate that DNAM-1 regulates Treg cell function via TIGIT signaling and thus, it is a potential molecular target for augmenting Treg function in inflammatory diseases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNAM-1; Foxp3; mTORC1; Regulatory T (Treg) cells; TIGIT
语种	英语
scopus关键词	mammalian target of rapamycin complex 1; protein kinase B; transcription factor FOXP3; CD226 antigen; forkhead transcription factor; Foxp3 protein, mouse; immunoglobulin receptor; mTOR protein, mouse; poliovirus receptor; protein binding; protein kinase B; T cell Ig and ITIM domain protein, mouse; T lymphocyte antigen; target of rapamycin kinase; virus receptor; animal cell; animal experiment; animal model; animal tissue; Article; CD155 gene; cell function; cell transfer; controlled study; DNAM 1 gene; down regulation; Foxp3 gene; gene; gene control; gene expression; graft versus host reaction; immunopathogenesis; inflammation; intracellular signaling; mouse; nonhuman; protein binding; regulatory T lymphocyte; TIGIT gene; adoptive transfer; animal; Bagg albino mouse; C57BL mouse; gene expression regulation; genetics; graft versus host reaction; human; immunological tolerance; immunology; pathology; regulatory T lymphocyte; signal transduction; transplantation; whole body radiation; Adoptive Transfer; Animals; Antigens, Differentiation, T-Lymphocyte; Forkhead Transcription Factors; Gene Expression Regulation; Graft vs Host Disease; Humans; Immune Tolerance; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Protein Binding; Proto-Oncogene Proteins c-akt; Receptors, Immunologic; Receptors, Virus; Signal Transduction; T-Lymphocytes, Regulatory; TOR Serine-Threonine Kinases; Whole-Body Irradiation
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/251174
作者单位	Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan; Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, 305-8575, Japan; R&D Center for Innovative Drug Discovery, University of Tsukuba, Tsukuba, 305-8575, Japan; TNAX Biopharma Corporation, Tsukuba, 305-8575, Japan; PhD Program in Human Biology, University of Tsukuba, Tsukuba, 305-8575, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, 305-8575, Japan; Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8577, Japan; Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W1R7, Canada; Central Institute for Experimental Animals, Kanagawa, 210-0821, Japan
推荐引用方式 GB/T 7714	Sato K.,Yamashita-Kanemaru Y.,Abe F.,et al. DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions[J],2021,118(21).
APA	Sato K..,Yamashita-Kanemaru Y..,Abe F..,Murata R..,Nakamura-Shinya Y..,...&Shibuya K..(2021).DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions.Proceedings of the National Academy of Sciences of the United States of America,118(21).
MLA	Sato K.,et al."DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021).