{"doi":"10.1126/sciadv.add6165","title":"RNA binding protein DDX5 restricts RORγt <sup>+</sup> T <sub>reg</sub> 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 + T reg suppressor activities and are better protected from intestinal inflammation. Genetic ablation or pharmacologic inhibition of HIF1α restores enteropathy susceptibility in DDX5 ΔT mice. The DDX5–HIF1α–IL-10 pathway is conserved in mice and humans. These findings reveal potential therapeutic targets for intestinal inflammatory diseases.","journal":"Science Advances","year":2023,"id":335905,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":84650,"name":"Qiyuan Yang","orcid":"0000-0001-6204-9094","position":1,"is_corresponding":false},{"id":571407,"name":"Nicholas Chen","orcid":"0000-0003-1919-9059","position":2,"is_corresponding":false},{"id":571408,"name":"Anna Zheng","orcid":"0000-0002-8431-6584","position":3,"is_corresponding":false},{"id":492031,"name":"Nazia Abbasi","orcid":"0000-0002-7686-4847","position":4,"is_corresponding":false},{"id":23911,"name":"Gaowei Wang","orcid":null,"position":5,"is_corresponding":false},{"id":492034,"name":"Parth Patel","orcid":"0000-0002-2248-7281","position":6,"is_corresponding":false},{"id":493041,"name":"Benjamin S. Cho","orcid":null,"position":7,"is_corresponding":false},{"id":43217,"name":"Brian A. Yee","orcid":"0000-0001-5615-8550","position":8,"is_corresponding":false},{"id":288847,"name":"Lunfeng Zhang","orcid":"0000-0002-5978-7157","position":9,"is_corresponding":false},{"id":280720,"name":"Hiutung Chu","orcid":"0000-0001-7489-0446","position":10,"is_corresponding":false},{"id":288852,"name":"Sylvia Μ. Evans","orcid":"0000-0001-5035-3697","position":11,"is_corresponding":false},{"id":43290,"name":"G Yeo","orcid":null,"position":12,"is_corresponding":false},{"id":267199,"name":"Ye Zheng","orcid":"0000-0001-5012-4309","position":13,"is_corresponding":false},{"id":242484,"name":"Wendy Huang","orcid":"0000-0001-7425-8280","position":14,"is_corresponding":false},{"id":571406,"name":"Shengyun Ma","orcid":"0000-0003-3368-9388","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:10:02.777338Z","pmid":"36724232","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}