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| Status |
Public on Feb 05, 2019 |
| Title |
Retinoic acid receptor alpha represses a Th9 transcriptional and epigenomic program to reduce allergic pathology |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
T helper (Th) differentiation is regulated by diverse inputs including the Vitamin A metabolite retinoic acid (RA). RA acts through its receptor RAR to repress transcription of inflammatory cytokines, but it is also essential for Th-mediated immunity, pointing to complex effects of RA in Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during differentiation of CD4+ T cells to multiple Th subsets. RA effects were subset-selective, and quantitatively greatest in Th9 cells. RA globally antagonized Th9-promoting transcription factors (TFs) and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARa. RA-RARaactivity limited Th9-associated pulmonary inflammation in mice, and allergic inflammation in humans was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARa signaling in Th differentiation, arguing for a role for RA in IL-9 related diseases.
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| Overall design |
Integrated analysis of epigenome and transcriptome data from Th subsets treated with vehicle control or retinoic acid, and of in vivo Th subsets from papain-sensitized mice
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| Contributor(s) |
Schwartz DS, Meylan F, Shih HY, Mikami Y, Petermann FP, Sun HW, Yao CY, Jiang K, Davis FP, Kanno Y, O'Shea JJ |
| Citation(s) |
30650370 |
| Submission date |
Dec 07, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Hong-wei Sun |
| Organization name |
NIAMS
|
| Department |
Office of Science & Technology
|
| Lab |
Biodata Mining & Discovery Section
|
| Street address |
9000 Rockville Pile
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (136)
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| Relations |
| BioProject |
PRJNA508954 |
| SRA |
SRP173192 |
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