{"doi":"10.1084/jem.20241463","title":"REV-ERB regulates RORγt+ regulatory T cell specification and function through the Bhlhe40-c-Maf axis","abstract":"Foxp3+ regulatory T (Treg) cells co-expressing RORγt adopt specialized functions to restrain intestinal inflammation. However, despite extensive characterization, the factors governing RORγt+Foxp3+ Treg specialization remain unclear. Here, we report that transcriptional repressor REV-ERB is critical for the differentiation and function of colonic RORγt+Foxp3+ Treg cells. REV-ERB deficiency exacerbates both TNBS- and oxazolone-induced intestinal inflammation. Mechanistically, REV-ERB promotes RORγt expression through suppressing the expression of transcriptional repressor Bhlhe40, which in turn inhibits c-Maf, a key factor promoting colonic RORγt+Foxp3+ Treg differentiation and function. Moreover, this Bhlhe40-c-Maf axis downstream of REV-ERB also regulates the expression of core colonic Treg signature genes including IL-10 and CTLA-4, while REV-ERB additionally safeguards RORγt+Foxp3+ Treg functional stability by directly suppressing proinflammatory cytokine IL-17A production. Collectively, the present study identifies that REV-ERB along with the downstream Bhlhe40-c-Maf axis jointly controls the RORγt+Foxp3+ Treg differentiation and suppressive function, suggesting that modulating their activities may strengthen RORγt+Foxp3+ Treg function to ameliorate inflammatory bowel diseases.","journal":"The Journal of Experimental Medicine","year":2025,"id":535690,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":446133,"name":"Zhi Liu","orcid":"0009-0000-3299-0289","position":1,"is_corresponding":false},{"id":1419820,"name":"Yao Li","orcid":"0009-0008-1296-3521","position":2,"is_corresponding":false},{"id":1419821,"name":"Yannan You","orcid":"0000-0002-8553-6394","position":3,"is_corresponding":false},{"id":1419822,"name":"Kaiye Yue","orcid":"0000-0002-1352-6912","position":4,"is_corresponding":false},{"id":267196,"name":"Yuqiong Liang","orcid":"0009-0007-1242-7115","position":5,"is_corresponding":false},{"id":267195,"name":"Chin-San Loo","orcid":"0000-0001-7915-2995","position":6,"is_corresponding":false},{"id":550353,"name":"Jingting Yu","orcid":"0009-0005-1182-3680","position":7,"is_corresponding":false},{"id":1419823,"name":"Matthias Leblanc","orcid":"0009-0005-8669-959X","position":8,"is_corresponding":false},{"id":1419824,"name":"Dehui Wang","orcid":"0000-0003-0346-3193","position":9,"is_corresponding":false},{"id":704614,"name":"Huabin Li","orcid":"0000-0002-2477-2879","position":10,"is_corresponding":false},{"id":267199,"name":"Ye Zheng","orcid":"0000-0001-5012-4309","position":11,"is_corresponding":false},{"id":1419819,"name":"Xingrong Hu","orcid":"0009-0002-3904-939X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:52:00.885532Z","pmid":"41359309","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":[]}