| First Author | Singh AK | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4515 |
| PubMed ID | 30375383 | Mgi Jnum | J:268526 |
| Mgi Id | MGI:6267977 | Doi | 10.1038/s41467-018-06924-5 |
| Citation | Singh AK, et al. (2018) SUMOylation of ROR-gammat inhibits IL-17 expression and inflammation via HDAC2. Nat Commun 9(1):4515 |
| abstractText | Dysregulated ROR-gammat-mediated IL-17 transcription is central to the pathogenesis of several inflammatory disorders, yet the molecular mechanisms that govern the transcription factor activity of ROR-gammat in the regulation of IL-17 are not fully defined. Here we show that SUMO-conjugating enzyme Ubc9 interacts with a conserved GKAE motif in ROR-gammat to induce SUMOylation of ROR-gammat and suppress IL-17 expression. Th17 cells expressing SUMOylation-defective ROR-gammat are highly colitogenic upon transfer to Rag1(-/-) mice. Mechanistically, SUMOylation of ROR-gammat facilitates the binding of HDAC2 to the IL-17 promoter and represses IL-17 transcription. Mice with conditional deletion of HDAC2 in CD4(+) T cells have elevated IL-17 expression and severe colitis. The identification of the Ubc9/ROR-gammat/HDAC2 axis that governs IL-17 expression may open new venues for the development of therapeutic measures for inflammatory disorders. |
