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miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury

McGurran, Hugo, Kumbol, Victor, Krüger, Christina, Wallach, Thomas, Lehnardt, Seija·2024·Cells
DOI 10.3390/cells13050407PMC PMC10930870
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Abstract

Toll-like receptors (TLRs) are a collection of pattern recognition sensors that form a first line of defence by detecting pathogen- or damage-associated molecular patterns and initiating an inflammatory response. TLR activation in microglia, the major immune cells in the brain, can trigger the release of inflammatory molecules, which may contribute to various CNS diseases including Alzheimer’s disease. Recently, some microRNAs were shown to serve as signalling molecules for TLRs. Here, we present miR-154-5p as a novel TLR7 ligand. Exposing microglia to miR-154-5p results in cytokine release and alters expression of the TLR signalling pathway dependent on TLR7. Additionally, miR-154-5p causes neuronal injury in enriched cortical neuron cultures and additive toxicity in the presence of microglia. Finally, intrathecal injection of miR-154-5p into mice leads to neuronal injury and accumulation of microglia in the cerebral cortex dependent on TLR7 expression. In conclusion, this study establishes miR-154-5p as a direct activator of TLR7 that can cause neuroinflammation and neuronal injury, which may contribute to CNS disease.

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Metadata

Authors
McGurran, H., Kumbol, V., Krüger, C., Wallach, T., & Lehnardt, S.
Affiliations
  • Charité—Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, 10117 Berlin, Germany
  • 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
Venue
Cells
Publisher
MDPI AG
Published
2024-02-26
Volume
13
Issue
5
Pages
407
ISSN
2073-4409
DOI
10.3390/cells13050407
PMC
PMC10930870
Cited by
12
References
3
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Deutsche Forschungsgemeinschaft (SFB-TRR 167/B03, LE 2420/7-1)

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