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Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation

Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje n...

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Autores principales: Ridder, Kirsten, Keller, Sascha, Dams, Maria, Rupp, Anne-Kathleen, Schlaudraff, Jessica, Del Turco, Domenico, Starmann, Julia, Macas, Jadranka, Karpova, Darja, Devraj, Kavi, Depboylu, Candan, Landfried, Britta, Arnold, Bernd, Plate, Karl H., Höglinger, Günter, Sültmann, Holger, Altevogt, Peter, Momma, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043485/
https://www.ncbi.nlm.nih.gov/pubmed/24893313
http://dx.doi.org/10.1371/journal.pbio.1001874
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author Ridder, Kirsten
Keller, Sascha
Dams, Maria
Rupp, Anne-Kathleen
Schlaudraff, Jessica
Del Turco, Domenico
Starmann, Julia
Macas, Jadranka
Karpova, Darja
Devraj, Kavi
Depboylu, Candan
Landfried, Britta
Arnold, Bernd
Plate, Karl H.
Höglinger, Günter
Sültmann, Holger
Altevogt, Peter
Momma, Stefan
author_facet Ridder, Kirsten
Keller, Sascha
Dams, Maria
Rupp, Anne-Kathleen
Schlaudraff, Jessica
Del Turco, Domenico
Starmann, Julia
Macas, Jadranka
Karpova, Darja
Devraj, Kavi
Depboylu, Candan
Landfried, Britta
Arnold, Bernd
Plate, Karl H.
Höglinger, Günter
Sültmann, Holger
Altevogt, Peter
Momma, Stefan
author_sort Ridder, Kirsten
collection PubMed
description Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs) from blood cells contain Cre mRNA, which induces recombination in neurons when injected into the brain. Although Cre-mediated recombination events in the brain occur very rarely in healthy animals, their number increases considerably in different injury models, particularly under inflammatory conditions, and extend beyond Purkinje neurons to other neuronal populations in cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in their miRNA profile from their nonrecombined counterparts, indicating physiological significance. These observations reveal the existence of a previously unrecognized mechanism to communicate RNA-based signals between the hematopoietic system and various organs, including the brain, in response to inflammation.
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spelling pubmed-40434852014-06-09 Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation Ridder, Kirsten Keller, Sascha Dams, Maria Rupp, Anne-Kathleen Schlaudraff, Jessica Del Turco, Domenico Starmann, Julia Macas, Jadranka Karpova, Darja Devraj, Kavi Depboylu, Candan Landfried, Britta Arnold, Bernd Plate, Karl H. Höglinger, Günter Sültmann, Holger Altevogt, Peter Momma, Stefan PLoS Biol Research Article Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs) from blood cells contain Cre mRNA, which induces recombination in neurons when injected into the brain. Although Cre-mediated recombination events in the brain occur very rarely in healthy animals, their number increases considerably in different injury models, particularly under inflammatory conditions, and extend beyond Purkinje neurons to other neuronal populations in cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in their miRNA profile from their nonrecombined counterparts, indicating physiological significance. These observations reveal the existence of a previously unrecognized mechanism to communicate RNA-based signals between the hematopoietic system and various organs, including the brain, in response to inflammation. Public Library of Science 2014-06-03 /pmc/articles/PMC4043485/ /pubmed/24893313 http://dx.doi.org/10.1371/journal.pbio.1001874 Text en © 2014 Ridder et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ridder, Kirsten
Keller, Sascha
Dams, Maria
Rupp, Anne-Kathleen
Schlaudraff, Jessica
Del Turco, Domenico
Starmann, Julia
Macas, Jadranka
Karpova, Darja
Devraj, Kavi
Depboylu, Candan
Landfried, Britta
Arnold, Bernd
Plate, Karl H.
Höglinger, Günter
Sültmann, Holger
Altevogt, Peter
Momma, Stefan
Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
title Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
title_full Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
title_fullStr Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
title_full_unstemmed Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
title_short Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
title_sort extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043485/
https://www.ncbi.nlm.nih.gov/pubmed/24893313
http://dx.doi.org/10.1371/journal.pbio.1001874
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