| First Author | Ma S | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 11 | Pages | 110520 |
| PubMed ID | 35294872 | Mgi Jnum | J:324904 |
| Mgi Id | MGI:7281975 | Doi | 10.1016/j.celrep.2022.110520 |
| Citation | Ma S, et al. (2022) RORgammat phosphorylation protects against T cell-mediated inflammation. Cell Rep 38(11):110520 |
| abstractText | RAR-related orphan receptor-gamma (RORgammat) is an essential transcription factor for thymic T cell development, secondary lymphoid tissue organogenesis, and peripheral immune cell differentiation. Serine 182 phosphorylation is a major post-translational modification (PTM) on RORgammat. However, the in vivo contribution of this PTM in health and disease settings is unclear. We report that this PTM is not involved in thymic T cell development and effector T cell differentiation. Instead, it is a critical regulator of inflammation downstream of IL-1beta signaling and extracellular signal regulated kinases (ERKs) activation. ERKs phosphorylation of serine 182 on RORgammat serves to simultaneously restrict Th17 hyperactivation and promote anti-inflammatory cytokine IL-10 production in RORgammat(+) Treg cells. Phospho-null RORgammat(S182A) knockin mice experience exacerbated inflammation in models of colitis and experimental autoimmune encephalomyelitis (EAE). In summary, the IL-1beta-ERK-RORgammat(S182) circuit protects against T cell-mediated inflammation and provides potential therapeutic targets to combat autoimmune diseases. |
