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Publication

RORγt phosphorylation protects against T cell-mediated inflammation.

Cell reports | 2022

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.

Pubmed ID: 35294872 RIS Download

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Associated grants

Agency: BLRD VA, United States
Id: I01 BX005106
Agency: BLRD VA, United States
Id: I01 BX004594
Agency: NIAID NIH HHS, United States
Id: R01 AI129973
Agency: NIDDK NIH HHS, United States
Id: P30 DK120515
Agency: NIAAA NIH HHS, United States
Id: R01 AA024726
Agency: NIH HHS, United States
Id: S10 OD026929
Agency: NIAAA NIH HHS, United States
Id: U01 AA026939
Agency: NIAID NIH HHS, United States
Id: P01 AI132122
Agency: NIDDK NIH HHS, United States
Id: R01 DK091183
Agency: NIAAA NIH HHS, United States
Id: R37 AA020703
Agency: NCI NIH HHS, United States
Id: P30 CA023100
Agency: NIGMS NIH HHS, United States
Id: R01 GM124494

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