RNA binding protein DDX5 restricts RORγt⁺ T_reg suppressor function to promote intestine inflammation.

ABSTRACT: Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt⁺ T_regs) play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part by secreting the anti-inflammation cytokine interleukin-10 (IL-10). Here, we report that hypoxia-induced factor 1α (HIF1α) is the master transcription factor for Il10 in RORγt⁺ T_regs. This critical anti-inflammatory pathway is negatively regulated by an RNA binding protein DEAD box helicase 5 (DDX5). As a transcriptional corepressor, DDX5 restricts the expression of HIF1α and its downstream target gene Il10 in RORγt⁺ T_regs. T cell-specific Ddx5 knockout (DDX5^ΔT) mice have augmented RORγt⁺

SUBMITTER: Ma S 

PROVIDER: S-EPMC9891705 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature