{"doi":"10.1084/jem.20250573","title":"RORγt eTACs mediate oral tolerance and Treg induction","abstract":"The immune system must distinguish pathogens from innocuous dietary antigens, but the precise mechanisms and cellular actors remain unclear. Here, we demonstrate that RORγt-lineage APCs are required for oral tolerance. Using lineage tracing and single-cell sequencing, we show these APCs consist of three principal populations: type 3 innate lymphoid cells (ILC3s), RORγt-lineage dendritic cells, and cells expressing Aire called RORγt eTACs (R-eTACs)-also known as Janus or Thetis cells. We show that R-eTACs, but not ILC3s, are required for oral tolerance induction. We find R-eTACs are of probable myeloid origin and uniquely express integrin β8 (Itgb8). Both MHCII and Itgb8 expression in RORγt-lineage cells are necessary to induce food-specific regulatory T cells. Mice lacking R-eTACs or with deletion of MHCII or Itgb8 in the RORγt lineage fail to generate Tregs and instead develop a T-follicular helper response with elevated antigen-specific antibodies. These findings establish R-eTACs as critical mediators of oral tolerance and suggest novel cellular targets to modulate immune tolerance.","journal":"The Journal of Experimental Medicine","year":2025,"id":509465,"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":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"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":1084629,"name":"Anita Qualls","orcid":"0000-0003-0576-8863","position":1,"is_corresponding":false},{"id":1169842,"name":"Han Yin","orcid":"0009-0007-5721-3022","position":2,"is_corresponding":false},{"id":677160,"name":"Jiaxi Wang","orcid":"0000-0001-6043-9953","position":3,"is_corresponding":false},{"id":1111647,"name":"Matthew P. Arvedson","orcid":"0000-0001-7717-0188","position":4,"is_corresponding":false},{"id":841689,"name":"Joe Germino","orcid":"0000-0003-3939-3342","position":5,"is_corresponding":false},{"id":1309674,"name":"Nolan K. Horner","orcid":"0009-0004-9388-5676","position":6,"is_corresponding":false},{"id":1363534,"name":"Sheng Zhong","orcid":"0009-0000-6178-4505","position":7,"is_corresponding":false},{"id":1363535,"name":"Juan Du","orcid":"0000-0001-7428-0576","position":8,"is_corresponding":false},{"id":467965,"name":"Martín Valdearcos","orcid":"0000-0002-5784-2458","position":9,"is_corresponding":false},{"id":58988,"name":"Vasilis Ntranos","orcid":"0000-0002-2477-0670","position":10,"is_corresponding":false},{"id":80235,"name":"Richard M. Locksley","orcid":"0000-0002-5468-6867","position":11,"is_corresponding":false},{"id":80220,"name":"Roberto R. Ricardo-Gonzalez","orcid":"0000-0002-6135-4035","position":12,"is_corresponding":false},{"id":73995,"name":"James M. Gardner","orcid":"0000-0003-3470-9520","position":13,"is_corresponding":false},{"id":228361,"name":"Im‐Hong Sun","orcid":"0000-0003-0288-2062","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:47:24.513904Z","pmid":"40298935","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":[]}