| First Author | Ma S | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 5 | Pages | eadd6165 |
| PubMed ID | 36724232 | Mgi Jnum | J:353483 |
| Mgi Id | MGI:7433782 | Doi | 10.1126/sciadv.add6165 |
| Citation | Ma S, et al. (2023) RNA binding protein DDX5 restricts RORgammat(+) T(reg) suppressor function to promote intestine inflammation. Sci Adv 9(5):eadd6165 |
| abstractText | Retinoid-related orphan receptor (RAR) gamma (RORgammat)-expressing regulatory T cells (RORgammat(+) 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 1alpha (HIF1alpha) is the master transcription factor for Il10 in RORgammat(+) 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 HIF1alpha and its downstream target gene Il10 in RORgammat(+) T(regs). T cell-specific Ddx5 knockout (DDX5(DeltaT)) mice have augmented RORgammat(+) T(reg) suppressor activities and are better protected from intestinal inflammation. Genetic ablation or pharmacologic inhibition of HIF1alpha restores enteropathy susceptibility in DDX5(DeltaT) mice. The DDX5-HIF1alpha-IL-10 pathway is conserved in mice and humans. These findings reveal potential therapeutic targets for intestinal inflammatory diseases. |
