| First Author | Zhong X | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 42 | Pages | eadc9221 |
| PubMed ID | 36269826 | Mgi Jnum | J:330635 |
| Mgi Id | MGI:7379703 | Doi | 10.1126/sciadv.adc9221 |
| Citation | Zhong X, et al. (2022) Decoupling the role of RORgammat in the differentiation and effector function of TH17 cells. Sci Adv 8(42):eadc9221 |
| abstractText | RORgammat is known to instruct the differentiation of T helper 17 (TH17) cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORgammat plays a distinct role in the differentiation and effector function of TH17 cells. Here, we show that mutation of RORgammat lysine-256, a ubiquitination site, to arginine (K256R) separates the RORgammat role in these two functions. Preventing ubiquitination at K256 via arginine substitution does not affect RORgammat-dependent thymocyte development, and TH17 differentiation in vitro and in vivo, however, greatly impaired the pathogenesis of TH17 cell-mediated experimental autoimmune encephalomyelitis (EAE). Mechanistically, K256R mutation impairs RORgammat to bind to and activate Runx1 expression critical for TH17-mediated EAE. Thus, RORgammat regulates the effector function of TH17 cells in addition to TH17 differentiation. This work informs the development of RORgammat-based therapies that specifically target the effector function of TH17 cells responsible for autoimmunity. |
