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Open AccessArticle

Identification of CNS Injury-Related microRNAs as Novel Toll-Like Receptor 7/8 Signaling Activators by Small RNA Sequencing

1
Institute of Cell Biology and Neurobiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
2
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
3
Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
4
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79106 Freiburg, Germany
5
Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
6
Department of Neurology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Cells 2020, 9(1), 186; https://doi.org/10.3390/cells9010186
Received: 3 December 2019 / Revised: 6 January 2020 / Accepted: 7 January 2020 / Published: 11 January 2020
(This article belongs to the Collection Regulatory Functions of microRNAs)
Toll-like receptors (TLRs) belong to pattern recognition receptors, which respond to danger signals such as pathogen-associated molecular patterns or damage-associated molecular patterns. Upon TLR activation in microglia, the major immune cells in the brain, distinct signaling cascades trigger the production of inflammatory molecules, being a critical feature in neuroinflammation and neurodegenerative processes. Recently, individual microRNAs (miRNAs) were shown to act as endogenous TLR ligands. Here, we conducted systematic screening for miRNAs as potential TLR7/8 ligands by small RNA sequencing of apoptotic neurons and their corresponding supernatants. Several miRNA species were identified in both supernatants and injured neurons, and 83.3% of the media-enriched miRNAs activated murine and/or human TLR7/8 expressed in HEK293-derived TLR reporter cells. Among the detected extracellular miRNAs, distinct miRNAs such as miR-340-3p and miR-132-5p induced cytokine and chemokine release from microglia and triggered neurotoxicity in vitro. Taken together, our systematic study establishes miRNAs released from injured neurons as new TLR7/8 activators, which contribute to inflammatory and neurodegenerative responses in the central nervous system (CNS). View Full-Text
Keywords: microRNA; toll-like receptor; microglia; neurons; neurodegeneration; small RNA sequencing microRNA; toll-like receptor; microglia; neurons; neurodegeneration; small RNA sequencing
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Wallach, T.; Wetzel, M.; Dembny, P.; Staszewski, O.; Krüger, C.; Buonfiglioli, A.; Prinz, M.; Lehnardt, S. Identification of CNS Injury-Related microRNAs as Novel Toll-Like Receptor 7/8 Signaling Activators by Small RNA Sequencing. Cells 2020, 9, 186.

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