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 re
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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Metadaten
Author:Kirsten Ridder, Sascha Keller, Maria Dams, Anne-Kathleen Rupp, Jessica Schlaudraff, Domenico Del Turco, Julia Starmann, Jadranka Macas, Darja Karpova, Kavi Devraj, Candan Depboylu, Britta Landfried, Bernd Arnold, Karl H. Plate, Günter Höglinger, Holger Sültmann, Peter Altevogt, Stefan Momma
URN:urn:nbn:de:hebis:30:3-332723
DOI:http://dx.doi.org/10.1371/journal.pbio.1001874
ISSN:1545-7885
ISSN:1544-9173
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24893313
Parent Title (English):PLoS biology
Publisher:Public Library of Science
Place of publication:Lawrence, KS
Document Type:Article
Language:English
Date of Publication (online):2014/06/03
Date of first Publication:2014/06/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/06/05
Volume:12
Issue:(6): e1001874
Pagenumber:15
Note:
Copyright: © 2014 Ridder et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:365061638
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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