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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 10, 2023 |
| Title |
TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
TPL2 (MAP3K8) is a central signaling node in the inflammatory response of peripheral immune cells. We find that TPL2 kinase activity modulates microglial cytokine release and is required for microglia-mediated neuron death in vitro. In acute in vivo neuroinflammation settings, TPL2 kinase activity regulates cytokine levels and activation states of microglia. In a tauopathy model of chronic neurodegeneration, loss of TPL2 kinase activity reduces neuroinflammation and rescues synapse loss, brain volume loss, and behavioral deficits. Single-cell RNAseq analysis indicates protection in the tauopathy model was associated with reductions in activated microglia subpopulations as well as infiltrating peripheral immune cells. Overall, using various models, we find that TPL2 kinase activity promotes multiple harmful consequences of microglial activation in the brain including cytokine release, iNOS induction, astrocyte activation, and immune cell infiltration. Consequently, inhibiting TPL2 kinase activity could represent a potential therapeutic strategy in neurodegenerative conditions.
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| Overall design |
~3-month-old WT or TPL2-KD mice were injected with PBS vehicle control or LPS (10 mg/kg) (n =5 per condition). 24 hours later, mice were perfused with cold PBS and the mouse hemi brains were immediately sub-dissected and preserved in RNAlater.
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| Contributor(s) |
Wang Y, Hanson JE |
| Citation(s) |
37555828 |
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| Submission date |
Feb 09, 2022 |
| Last update date |
Aug 10, 2023 |
| Contact name |
Brad A Friedman |
| Organization name |
Genentech, Inc.
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| Department |
Neuroinformatics
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| Street address |
1 DNA Way
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| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94133 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (18)
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| GSM5880309 |
TPL2KD mice, LPS treated, rep4 |
| GSM5880310 |
TPL2KD mice, vehicle treated, rep1 |
| GSM5880311 |
TPL2KD mice, vehicle treated, rep2 |
| GSM5880312 |
TPL2KD mice, vehicle treated, rep3 |
| GSM5880313 |
TPL2KD mice, vehicle treated, rep4 |
| GSM5880314 |
WT mice, LPS treated, rep1 |
| GSM5880315 |
WT mice, LPS treated, rep2 |
| GSM5880316 |
WT mice, LPS treated, rep3 |
| GSM5880317 |
WT mice, LPS treated, rep4 |
| GSM5880318 |
WT mice, LPS treated, rep5 |
| GSM5880319 |
WT mice, vehicle treated, rep1 |
| GSM5880320 |
WT mice, vehicle treated, rep2 |
| GSM5880321 |
WT mice, vehicle treated, rep3 |
| GSM5880322 |
WT mice, vehicle treated, rep4 |
| GSM5880323 |
WT mice, vehicle treated, rep5 |
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| Relations |
| BioProject |
PRJNA804717 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE196401_raw_counts.rData.gz |
3.6 Mb |
(ftp)(http) |
RDATA |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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