南方科技大学知识苑(SUSTech KC): The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation

题名	The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation
作者	Gatsiou，Aikaterini 1,2; Tual-Chalot，Simon 1; Napoli，Matteo 3; Ortega-Gomez，Almudena 4; Regen，Tommy 5; Badolia，Rachit 6; Cesarini，Valeriana 7; Garcia-Gonzalez，Claudia 8; Chevre，Raphael 4,9; Ciliberti，Giorgia 10; Silvestre-Roig，Carlos 4,9; Martini，Maurizio 11,12; Hoffmann，Jedrzej 13; Hamouche，Rana 6; Visker，Joseph R.6; Diakos，Nikolaos 6; Wietelmann，Astrid 8; Silvestris，Domenico Alessandro 7; Georgiopoulos，Georgios 14,25; Moshfegh，Ali 15,16; Schneider，Andre 8; Chen，Wei17,18 ; Guenther，Stefan 8; Backs，Johannes 19,20; Kwak，Shin 21; Selzman，Craig H.6,22; Stamatelopoulos，Kimon 14,25; Rose-John，Stefan 23; Trautwein，Christian 24; Spyridopoulos，Ioakim 25,26; Braun，Thomas 8; Waisman，Ari 5; Gallo，Angela 7; Drakos，Stavros G.6,27; Dimmeler，Stefanie 28,30; Sperandio，Markus 3,31; Soehnlein，Oliver 4,9,31,32; Stellos，Konstantinos 1,2,10,20,29
通讯作者	Gatsiou，Aikaterini; Stellos，Konstantinos
发表日期	2023-05-09
DOI	10.1016/j.immuni.2023.03.021
发表期刊	Immunity 影响因子和分区
ISSN	1074-7613
EISSN	1097-4180
卷号	56 期号:5页码:979-997.e11
摘要	Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution of intrinsic RNA nucleotide modifications to this response remains elusive. We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. Genetic ablation of ADAR2 from vascular endothelial cells diminished myeloid cell rolling and adhesion on vascular walls and reduced immune cell infiltration within ischemic tissues. ADAR2 was required in the endothelium for the expression of the IL-6 receptor subunit, IL-6 signal transducer (IL6ST; gp130), and subsequently, for IL-6 trans-signaling responses. ADAR2-induced adenosine-to-inosine RNA editing suppressed the Drosha-dependent primary microRNA processing, thereby overwriting the default endothelial transcriptional program to safeguard gp130 expression. This work demonstrates a role for ADAR2 epitranscriptional activity as a checkpoint in IL-6 trans-signaling and immune cell trafficking to sites of tissue injury.
关键词	ADAR2 Endothelial Cells Epitranscriptome Gene Expression IL-6 Immune Cell Trafficking Ischemia MicroRNAs RNA Editing RNA Modifications
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
重要成果	NI论文
学校署名	其他
资助项目	Deutsche Forschungsgemeinschaft[394046768] ; Deutsche Forschungsgemeinschaft[75732319] ; Deutsche Forschungsgemeinschaft[CRC1382/403224013] ; Deutsche Forschungsgemeinschaft[SFB TR285/10-2] ; Deutsche Forschungsgemeinschaft[SFB1366]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:001006062300001
出版者	CELL PRESS
ESI学科分类	IMMUNOLOGY
Scopus记录号	2-s2.0-85154621202
来源库	Scopus
引用统计	被引频次[WOS]：11
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/536529
专题	生命科学学院_生物系生命科学学院前沿与交叉科学研究院
作者单位	1.Biosciences Institute,Vascular Biology and Medicine Theme,Faculty of Medical Sciences,Newcastle University,Newcastle upon Tyne,United Kingdom 2.RNA Metabolism and Vascular Inflammation Laboratory,Institute of Cardiovascular Regeneration and Department of Cardiology,JW Goethe University Frankfurt,Frankfurt am Main,Germany 3.Institute for Cardiovascular Physiology and Pathophysiology,Walter Brendel Center for Experimental Medicine Biomedical Center (BMC),Ludwig-Maximilians-Universität München,Munich,Germany 4.Institute for Cardiovascular Prevention (IPEK),LMU Munich Hospital,Munich,Germany 5.Institute for Molecular Medicine,University Medical Center of the Johannes Gutenberg University of Mainz,Mainz,Germany 6.Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI),University of Utah School of Medicine,Salt Lake City,United States 7.Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy,Bambino Gesù Children's Hospital,IRCCS,Rome,Italy 8.Max-Planck Institute for Heart and Lung Research,Bad Nauheim,Germany 9.Institute for Experimental Pathology (ExPat),Center for Molecular Biology of Inflammation,WWU Muenster,Muenster,Germany 10.Department of Cardiovascular Research,European Center for Angioscience (ECAS),Heidelberg University,Mannheim,Germany 11.Fondazione Policlinico Universitario “A. Gemelli,” IRCCS,UOC Anatomia Patologica,Rome,Italy 12.Istituto di Anatomia Patologica,Università Cattolica del Sacro Cuore,Rome,Italy 13.Department of Cardiology,Goethe University Hospital Frankfurt,Frankfurt am Main,Germany 14.Department of Clinical Therapeutics,Alexandra Hospital,National and Kapodistrian University of Athens Medical School,Athens,Greece 15.Kancera AB,Stockholm,Sweden 16.Department of Oncology and Pathology at Karolinska Institutet,Stockholm,Sweden 17.Department of Biology,Southern University of Science and Technology,Shenzhen,Guangdong,China 18.Medi-X Institute,SUSTech Academy for Advanced Interdisciplinary Studies,Southern University of Science and Technology,Shenzhen,Guangdong,China 19.Institute of Experimental Cardiology,University Hospital Heidelberg,Heidelberg,Germany 20.German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung,DZHK),Heidelberg/Mannheim Partner Site,Heidelberg and Mannheim,Germany 21.Department of Molecular Neuropathogenesis,Tokyo Medical University,Tokyo,Japan 22.Division of Cardiothoracic Surgery,University of Utah School of Medicine,Salt Lake City,United States 23.Institute of Biochemistry,Christian-Albrechts-University Kiel,Kiel,Germany 24.Department of Internal Medicine III,University Hospital RWTH Aachen,Aachen,Germany 25.Translational Research Institute,Vascular Biology and Medicine Theme,Faculty of Medical Sciences,Newcastle University,Newcastle upon Tyne,United Kingdom 26.Department of Cardiology,Freeman Hospital,Newcastle upon Tyne NHS Foundation Trust,Newcastle upon Tyne,United Kingdom 27.Division of Cardiovascular Medicine,University of Utah School of Medicine,Salt Lake City,United States 28.Institute of Cardiovascular Regeneration,Center of Molecular Medicine,JW Goethe University Frankfurt,Frankfurt am Main,Germany 29.Cardio-Pulmonary Institute (CPI),Frankfurt am Main,Germany 30.German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung,DZHK),Frankfurt Partner Site,Germany 31.German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung,DZHK),Munich Heart Alliance Partner Site,Munich,Germany 32.Department of Physiology and Pharmacology (FyFa),Karolinska Institutet,Stockholm,Sweden
推荐引用方式 GB/T 7714	Gatsiou，Aikaterini,Tual-Chalot，Simon,Napoli，Matteo,et al. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation[J]. Immunity,2023,56(5):979-997.e11.
APA	Gatsiou，Aikaterini.,Tual-Chalot，Simon.,Napoli，Matteo.,Ortega-Gomez，Almudena.,Regen，Tommy.,...&Stellos，Konstantinos.(2023).The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation.Immunity,56(5),979-997.e11.
MLA	Gatsiou，Aikaterini,et al."The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation".Immunity 56.5(2023):979-997.e11.