| First Author | Chi X | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 11 | Pages | 109682 |
| PubMed ID | 34525365 | Mgi Jnum | J:323837 |
| Mgi Id | MGI:6876928 | Doi | 10.1016/j.celrep.2021.109682 |
| Citation | Chi X, et al. (2021) RORalpha is critical for mTORC1 activity in T cell-mediated colitis. Cell Rep 36(11):109682 |
| abstractText | Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells, among which a large portion of patients are resistant to current anti-inflammatory regimes. The mechanisms underlying colitis pathogenicity and drug resistance are not fully understood. Here, we demonstrate that RORalpha is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Roralpha deficiency in CD4(+) T cells greatly reduced colitis development. Mechanistically, RORalpha regulated T cell infiltration in colon and inhibited T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORalpha promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, is necessary for T cell-mediated colitis. Our results thus demonstrate a crucial role of the RORalpha-mTORC1 axis in CD4(+) T cells in promoting IBD, which may be targeted in human patients. |
