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Your Environment. Your Health.

Dataset Details

Superfund Research Program

Title: The nuclear receptor REV-ERBa modulates Th17 cell differentiation and function by competing with RORgt

Accession Number: GSE72271

Link to Dataset:

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Genome binding/occupancy profiling by high throughput sequencing

Organism(s): Mus musculus

Summary: T helper 17 (Th17) cells produce interleukin-17 (IL-17) cytokines and drive inflammatory responses in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. The differentiation of Th17 cells is dependent on the retinoic acid receptor-related orphan nuclear receptor RORgt. Here we identify REV-ERBa (encoded by Nr1d1), a member of the nuclear hormone receptor family (NHR), as a transcriptional repressor that antagonizes RORgt function in Th17 cells. REV-ERBa binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of RORgt-dependent genes such as Il17a and Il17f. Furthermore, elevated REV-ERBa expression or treatment with a synthetic REV-ERB agonist significantly delays the onset and impedes the progression of experimental autoimmune encephalomyelitis (EAE), a Th17 cell-mediated autoimmune disease. These results suggest that modulating REV-ERB activity may hold therapeutic potential for treatment of Th17 cell-mediated autoimmune diseases.

Publication(s) associated with this dataset:
  • Chang C, Loo C, Zhao X, Solt LA, Liang Y, Bapat SP, Cho H, Kamenecka TM, Leblanc M, Atkins AR, Yu RT, Downes M, Burris TP, Evans RM, Zheng Y. 2019. The nuclear receptor REV-ERB alpha modulates Th17 cell-mediated autoimmune disease. Proc Natl Acad Sci U S A 116:18528-18536. doi:10.1073/pnas.1907563116 PMID:31455731 PMCID:PMC6744854
Project(s) associated with this dataset:
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