Publication Date
5-5-2023
Journal
Science Advances
DOI
10.1126/sciadv.add2676
PMID
37146150
PMCID
PMC10162677
PubMedCentral® Posted Date
5-5-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Mice, Animals, Microglia, Mice, Knockout, Brain, Demyelinating Diseases, Cell Proliferation, Membrane Proteins, Nerve Tissue Proteins, Membrane Glycoproteins, Receptors, Immunologic
Abstract
TMEM106B, a lysosomal transmembrane protein, has been closely associated with brain health. Recently, an intriguing link between TMEM106B and brain inflammation has been discovered, but how TMEM106B regulates inflammation is unknown. Here, we report that TMEM106B deficiency in mice leads to reduced microglia proliferation and activation and increased microglial apoptosis in response to demyelination. We also found an increase in lysosomal pH and a decrease in lysosomal enzyme activities in TMEM106B-deficient microglia. Furthermore, TMEM106B loss results in a significant decrease in the protein levels of TREM2, an innate immune receptor essential for microglia survival and activation. Specific ablation of TMEM106B in microglia results in similar microglial phenotypes and myelination defects in mice, supporting the idea that microglial TMEM106B is critical for proper microglial activities and myelination. Moreover, the