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The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation.
Gatsiou, Aikaterini; Tual-Chalot, Simon; Napoli, Matteo; Ortega-Gomez, Almudena; Regen, Tommy; Badolia, Rachit; Cesarini, Valeriana; Garcia-Gonzalez, Claudia; Chevre, Raphael; Ciliberti, Giorgia; Silvestre-Roig, Carlos; Martini, Maurizio; Hoffmann, Jedrzej; Hamouche, Rana; Visker, Joseph R; Diakos, Nikolaos; Wietelmann, Astrid; Silvestris, Domenico Alessandro; Georgiopoulos, Georgios; Moshfegh, Ali; Schneider, Andre; Chen, Wei; Guenther, Stefan; Backs, Johannes; Kwak, Shin; Selzman, Craig H; Stamatelopoulos, Kimon; Rose-John, Stefan; Trautwein, Christian; Spyridopoulos, Ioakim; Braun, Thomas; Waisman, Ari; Gallo, Angela; Drakos, Stavros G; Dimmeler, Stefanie; Sperandio, Markus; Soehnlein, Oliver; Stellos, Konstantinos.
Afiliación
  • Gatsiou A; Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; RNA Metabolism and Vascular Inflammation Laboratory, Institute of Cardiovascular Regeneration and Department of Cardiology, JW Goethe University Frankfurt, Frankfur
  • Tual-Chalot S; Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Napoli M; Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.
  • Ortega-Gomez A; Institute for Cardiovascular Prevention (IPEK), LMU Munich Hospital, Munich, Germany.
  • Regen T; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
  • Badolia R; Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Cesarini V; Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Garcia-Gonzalez C; Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • Chevre R; Institute for Cardiovascular Prevention (IPEK), LMU Munich Hospital, Munich, Germany; Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation, WWU Muenster, Muenster, Germany.
  • Ciliberti G; Department of Cardiovascular Research, European Center for Angioscience (ECAS), Heidelberg University, Mannheim, Germany.
  • Silvestre-Roig C; Institute for Cardiovascular Prevention (IPEK), LMU Munich Hospital, Munich, Germany; Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation, WWU Muenster, Muenster, Germany.
  • Martini M; Fondazione Policlinico Universitario "A. Gemelli," IRCCS, UOC Anatomia Patologica, Rome, Italy; Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Hoffmann J; Department of Cardiology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
  • Hamouche R; Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Visker JR; Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Diakos N; Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Wietelmann A; Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • Silvestris DA; Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Georgiopoulos G; Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece; Translational Research Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Moshfegh A; Kancera AB, Stockholm, Sweden; Department of Oncology and Pathology at Karolinska Institutet, Stockholm, Sweden.
  • Schneider A; Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • Chen W; Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China; Medi-X Institute, SUSTech Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • Guenther S; Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • Backs J; Institute of Experimental Cardiology, University Hospital Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung, DZHK), Heidelberg/Mannheim Partner Site, Heidelberg and Mannheim, Germany.
  • Kwak S; Department of Molecular Neuropathogenesis, Tokyo Medical University, Tokyo, Japan.
  • Selzman CH; Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Cardiothoracic Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Stamatelopoulos K; Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece; Translational Research Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Rose-John S; Institute of Biochemistry, Christian-Albrechts-University Kiel, Kiel, Germany.
  • Trautwein C; Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Spyridopoulos I; Translational Research Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Department of Cardiology, Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Braun T; Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • Waisman A; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
  • Gallo A; Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Drakos SG; Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA; Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Dimmeler S; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, JW Goethe University Frankfurt, Frankfurt am Main, Germany; German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung, DZHK), Frankfurt Partner Site, Germany.
  • Sperandio M; Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Munich, Germany; German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung, DZHK), Munich Hear
  • Soehnlein O; Institute for Cardiovascular Prevention (IPEK), LMU Munich Hospital, Munich, Germany; Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation, WWU Muenster, Muenster, Germany; German Centre for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislauf-Forschung
  • Stellos K; Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; RNA Metabolism and Vascular Inflammation Laboratory, Institute of Cardiovascular Regeneration and Department of Cardiology, JW Goethe University Frankfurt, Frankfur
Immunity ; 56(5): 979-997.e11, 2023 05 09.
Article en En | MEDLINE | ID: mdl-37100060
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN / Interleucina-6 Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN / Interleucina-6 Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos