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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 31, 2010 |
| Title |
Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling: ChIPSeq |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity. Crucial for T helper17 (Th17) cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies.
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| Overall design |
Examination of Stat3 binding and H3K4me and H3Ac in helper T cells.
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| Contributor(s) |
Ghoreschi K, Laurence A, Yang X, Tato CM, McGeachy MJ, Konkel J, Ramos HL, Wei L, Davidson T, Bouladoux N, Grainger J, Chen Q, Kanno Y, Watford WT, Sun H, Eberl G, Shevach E, Belkaid Y, Cua DJ, Chen W, O'Shea JJ |
| Citation(s) |
20962846 |
| Submission date |
Aug 18, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Lai Wei |
| E-mail(s) |
weil2@mail.nih.gov
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| Phone |
3014961480
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| Organization name |
NIH/NEI/NCCAM
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| Street address |
10 Center Dr. Room 2B47
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (3) |
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| Relations |
| SRA |
SRP003810 |
| BioProject |
PRJNA130797 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23681_RAW.tar |
74.9 Mb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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