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| Status |
Public on Dec 21, 2020 |
| Title |
IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Tr1 deficient in TFs RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
IL-27 is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, Atf3) and 2 negative (Irf9, Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators Prdm1 and Maf that cooperatively drive the expression of signature genes induced by IL-27 in Type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3+regulatory T cells. Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying the ll10 deficient mice. Our work provides insights for IL-27 driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.
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| Overall design |
Bulk RNA-seq for in vitro derived Tr1 cells deficient in various transcription factors
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| |
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| Contributor(s) |
Madi A, Chihara N, Kuchroo V |
| Citation(s) |
33238123 |
| Submission date |
Sep 29, 2020 |
| Last update date |
Jan 04, 2021 |
| Contact name |
Vijay Kuchroo |
| Organization name |
Brigham & Women's Hospital
|
| Department |
Neurology
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| Lab |
Kuchroo
|
| Street address |
60 Fenwood Road
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
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| Samples (69)
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| This SubSeries is part of SuperSeries: |
| GSE159208 |
IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets |
|
| Relations |
| BioProject |
PRJNA666419 |
| SRA |
SRP285800 |
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