Loading...
UNC93B1 Is Widely Expressed in the Murine CNS and Is Required for Neuroinflammation and Neuronal Injury Induced by MicroRNA .
Klammer, Markus G Dzaye, Omar Wallach, Thomas Krüger, Christina Gaessler, Dorothea Buonfiglioli, Alice Derkow, Katja Kettenmann, Helmut Brinkmann, Melanie M Lehnardt, Seija
Klammer, Markus G
Dzaye, Omar
Wallach, Thomas
Krüger, Christina
Gaessler, Dorothea
Buonfiglioli, Alice
Derkow, Katja
Kettenmann, Helmut
Brinkmann, Melanie M
Lehnardt, Seija
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2021-09-13
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 5.8 MB
Other Titles
Abstract
The chaperone protein Unc-93 homolog B1 (UNC93B1) regulates internalization, trafficking, and stabilization of nucleic acid-sensing Toll-like receptors (TLR) in peripheral immune cells. We sought to determine UNC93B1 expression and its functional relevance in inflammatory and injurious processes in the central nervous system (CNS). We found that UNC93B1 is expressed in various CNS cells including microglia, astrocytes, oligodendrocytes, and neurons, as assessed by PCR, immunocyto-/histochemistry, and flow cytometry. UNC93B1 expression in the murine brain increased during development. Exposure to the microRNA let-7b, a recently discovered endogenous TLR7 activator, but also to TLR3 and TLR4 agonists, led to increased UNC93B1 expression in microglia and neurons. Microglial activation by extracellular let-7b required functional UNC93B1, as assessed by TNF ELISA. Neuronal injury induced by extracellular let-7b was dependent on UNC93B1, as UNC93B1-deficient neurons were unaffected by the microRNA's neurotoxicity in vitro. Intrathecal application of let-7b triggered neurodegeneration in wild-type mice, whereas mice deficient for UNC93B1 were protected against injurious effects on neurons and axons. In summary, our data demonstrate broad UNC93B1 expression in the murine brain and establish this chaperone as a modulator of neuroinflammation and neuronal injury triggered by extracellular microRNA and subsequent induction of TLR signaling.
Citation
Front Immunol. 2021 Sep 13;12:715774. doi: 10.3389/fimmu.2021.715774.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
1664-3224
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International