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| Status |
Public on Apr 10, 2020 |
| Title |
Epigenetic initiation of the Th17 differentiation programme is promoted by Cxxc finger protein 1 |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
IL-6/STAT3 signalling is known to initiate the Th17 differentiation programme, but the upstream regulatory mechanisms remain minimally explored. Here, we show that Cxxc finger protein 1 (Cxxc1) promoted the generation and stability of Th17 cells as an epigenetic regulator and prevented their differentiation into Treg cells. Mice with a T cell-specific deletion of Cxxc1 were protected from experimental autoimmune encephalomyelitis and were more susceptible to Citrobacter rodentium infection. Cxxc1-deficient T cells acquired a Treg cell-biased programme that dominantly suppressed Th17 cell generation via IL-6Rα production. Cxxc1 deficiency decreased IL-6Rα expression and impeded IL-6/STAT3 signalling, whereas the overexpression of IL-6Rα could reverse the defects seen in Cxxc1-deficient Th17 cells in vitro and in vivo. Genome-wide occupancy analysis revealed that Cxxc1 bound to Il6rα gene loci in the Th17 programme by maintaining the appropriate H3K4me3 modification of its promoter. Therefore, these data highlight that Cxxc1 as a key regulator governs the balance between Th17 and Treg cells by controlling the expression of IL-6Rα, which subsequently affects IL-6/STAT3 signalling and has a direct impact on Th17-related autoimmune diseases.
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| |
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| Overall design |
TH17 CHIP-SEQ
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| |
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| Contributor(s) |
Lie W, Lin F |
| Citation(s) |
31633019 |
| Submission date |
Jun 05, 2019 |
| Last update date |
Apr 11, 2020 |
| Contact name |
lie wang |
| E-mail(s) |
wanglie@zju.edu.cn
|
| Organization name |
zhejiang universiry
|
| Department |
immunology
|
| Street address |
Zijingang Campus, Zhejiang University，Yuhangtang Road 866
|
| City |
hangzhou |
| State/province |
zhejiang |
| ZIP/Postal code |
310058 |
| Country |
China |
| |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA546526 |
| SRA |
SRP200465 |
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