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- W4220784483 abstract "RAR-related orphan receptor-γ (RORγt) 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 RORγt. 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-1β signaling and extracellular signal regulated kinases (ERKs) activation. ERKs phosphorylation of serine 182 on RORγt serves to simultaneously restrict Th17 hyperactivation and promote anti-inflammatory cytokine IL-10 production in RORγt+ Treg cells. Phospho-null RORγtS182A knockin mice experience exacerbated inflammation in models of colitis and experimental autoimmune encephalomyelitis (EAE). In summary, the IL-1β-ERK-RORγtS182 circuit protects against T cell-mediated inflammation and provides potential therapeutic targets to combat autoimmune diseases." @default.
- W4220784483 created "2022-04-03" @default.
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- W4220784483 date "2022-03-01" @default.
- W4220784483 modified "2023-10-10" @default.
- W4220784483 title "RORγt phosphorylation protects against T cell-mediated inflammation" @default.
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- W4220784483 doi "https://doi.org/10.1016/j.celrep.2022.110520" @default.
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