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| Status |
Public on Apr 01, 2020 |
| Title |
Inhibition of glycolysis in pathogenic TH17 cells through targeting a miR-21-Peli1-c-Rel pathway prevents autoimmunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
It is well known that some pathogenic cells have enhanced glycolysis, the regulatory network leading to increased glycolysis are not well characterized. Here, we show that CNS-infiltrated pathogenic TH17 cells from diseased mice specifically upregulate glycolytic pathway genes compared to homeostatic intestinal TH17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro derived pathogenic TH17 cells are highly glycolytic compared to nonpathogenic TH17 cells. Chromatin landscape analyses demonstrate TH17 cells in vivo show distinct chromatin states, and pathogenic TH17 cells show enhanced chromatin accessibility at glycolytic genes with NF-kB binding sites. Mechanistic studies reveal that miR-21 targets the E3 ubiquitin ligase Peli1-c-Rel pathway to promote glucose metabolism of pathogenic TH17 cells. Therapeutic targeting c-Rel-mediated glycolysis in pathogenic TH17 cells represses autoimmune diseases. These findings extend our understanding of the regulation TH17 cell glycolysis in vivo and provide insights for future therapeutic intervention to TH17 cell mediated autoimmune diseases.
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| Overall design |
RNA-seq for ileum and CNS-infiltrated TH17 cells with two replicates. RNA-seq for c-Rel overexpression (Ad-c-Rel) and control (Ad-control) in TH17(β) cells in vitro with two replicates. RNA-seq for miR-21-/- and Control TH17(23) with two replicates. ATAC-seq for ileum and CNS-infiltrated TH17 cells with two replicates. ATAC-seq for TH17(β) and TH17(23) with two replicates.
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| Contributor(s) |
Yu X, Wang L, Han Z, Yao C, Hou G, Dai D, Jin W, Shen N |
| Citation(s) |
32414810 |
| |
| Submission date |
Mar 04, 2019 |
| Last update date |
Jul 14, 2020 |
| Contact name |
Zhijun Han |
| E-mail(s) |
hangeneral@126.com
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| Organization name |
Southern University of Science and Technology
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| Street address |
No 1088,xueyuan Rd., Nanshan District
|
| City |
Shenzhen |
| State/province |
Guangdong |
| ZIP/Postal code |
518055 |
| Country |
China |
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| Platforms (1) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA525358 |
| SRA |
SRP187402 |
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