miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury
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 relea...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/5/407 |
| _version_ | 1827319697469603840 |
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| author | Hugo McGurran Victor Kumbol Christina Krüger Thomas Wallach Seija Lehnardt |
| author_facet | Hugo McGurran Victor Kumbol Christina Krüger Thomas Wallach Seija Lehnardt |
| author_sort | Hugo McGurran |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T00:33:07Z |
| format | Article |
| id | doaj.art-2dcbe1135ee74be0ac30de315b14de64 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-25T00:33:07Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2dcbe1135ee74be0ac30de315b14de642024-03-12T16:41:36ZengMDPI AGCells2073-44092024-02-0113540710.3390/cells13050407miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal InjuryHugo McGurran0Victor Kumbol1Christina Krüger2Thomas Wallach3Seija Lehnardt4Charité—Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, 10117 Berlin, GermanyInstitute 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, GermanyInstitute 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, GermanyInstitute 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, GermanyToll-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.https://www.mdpi.com/2073-4409/13/5/407microRNAneurodegenerationneuroinflammationtoll-like receptorneuronsmicroglia |
| spellingShingle | Hugo McGurran Victor Kumbol Christina Krüger Thomas Wallach Seija Lehnardt miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury Cells microRNA neurodegeneration neuroinflammation toll-like receptor neurons microglia |
| title | miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury |
| title_full | miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury |
| title_fullStr | miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury |
| title_full_unstemmed | miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury |
| title_short | miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury |
| title_sort | mir 154 5p is a novel endogenous ligand for tlr7 inducing microglial activation and neuronal injury |
| topic | microRNA neurodegeneration neuroinflammation toll-like receptor neurons microglia |
| url | https://www.mdpi.com/2073-4409/13/5/407 |
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