{"doi":"10.1101/2025.09.09.675163","title":"<i>Trsp</i> is required by regulatory T cells to prevent lethal autoimmunity in mice","abstract":"Abstract Selenoproteins are involved in immune cell metabolism, yet the roles of these proteins in T cell development and function remain largely unknown. The Trsp gene encodes the selenocysteine tRNA (tRNA Sec ) required for translation of all selenoproteins. In this study, we found that Trsp was required for thymopoiesis, with the majority of tRNA Sec -deficient T cells not progressing beyond double negative 3 stage, with egressed thymocytes undergoing peripheral homeostatic expansion. Trsp- deficient CD4 + T cells exhibited impairments in TCR and IL-2 signaling and did not cause inflammation in experimental models. On the other hand, Trsp -deficient regulatory T (Treg) cells exhibited defects in suppressive function ex vivo and Treg-specific Trsp deletion using Trsp fl/fl Foxp3 YFP-Cre ( Trsp !ιTreg ) mice caused fatal autoimmunity similar to FOXP3-deficient mice. Reducing oxidative stress via 2-HOBA administration prolonged survival in these Trsp !ιTreg mice. These findings indicate that tRNA Sec is required for T cell homeostasis and may be therapeutic targets in inflammation. One sentence summary Trsp , a gene required for translation of all selenoproteins, is essential for all T cell development and function, especially regulatory T cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":574889,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"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":291498,"name":"Jennifer M. Pilat","orcid":"0000-0001-5385-3232","position":1,"is_corresponding":false},{"id":1482921,"name":"Anna Brooke Harris","orcid":null,"position":2,"is_corresponding":false},{"id":751896,"name":"Aaron Kwag","orcid":null,"position":3,"is_corresponding":false},{"id":1081211,"name":"Zaryab Aziz","orcid":null,"position":4,"is_corresponding":false},{"id":993730,"name":"Channing Chi","orcid":"0000-0003-4987-4764","position":5,"is_corresponding":false},{"id":1482922,"name":"Sam Schaefer","orcid":null,"position":6,"is_corresponding":false},{"id":675223,"name":"M. Diana Neely","orcid":"0000-0002-2141-0493","position":7,"is_corresponding":false},{"id":971286,"name":"Matthew A. Buendia","orcid":"0000-0002-1824-6266","position":8,"is_corresponding":false},{"id":1159911,"name":"Andrew P Pahnke","orcid":"0009-0000-2761-369X","position":9,"is_corresponding":false},{"id":291506,"name":"Christopher S. Williams","orcid":"0000-0002-1541-579X","position":10,"is_corresponding":false},{"id":1212550,"name":"Wentao Deng","orcid":"0009-0004-9903-9702","position":11,"is_corresponding":false},{"id":86848,"name":"M. Kay Washington","orcid":"0000-0002-9589-7695","position":12,"is_corresponding":false},{"id":107003,"name":"Jeffrey C. Rathmell","orcid":"0000-0002-4106-3396","position":13,"is_corresponding":false},{"id":338843,"name":"Charles R. Flynn","orcid":"0000-0002-3749-0598","position":14,"is_corresponding":false},{"id":1031242,"name":"Edmond H.H.M. Rings","orcid":"0000-0001-8195-4356","position":15,"is_corresponding":false},{"id":291497,"name":"Sarah P. Short","orcid":"0000-0001-9606-7370","position":16,"is_corresponding":false},{"id":350287,"name":"K. Sandeep Prabhu","orcid":"0000-0003-0644-1512","position":17,"is_corresponding":false},{"id":1031243,"name":"Janneke N. Samsom","orcid":"0000-0001-8054-3440","position":18,"is_corresponding":false},{"id":86846,"name":"Jeremy A. Goettel","orcid":"0000-0002-0749-2357","position":19,"is_corresponding":false},{"id":500518,"name":"Yash A. Choksi","orcid":"0000-0003-1717-4472","position":20,"is_corresponding":false},{"id":818980,"name":"Justin Jacobse","orcid":"0000-0002-1899-0319","position":0,"is_corresponding":true}],"reference_count":1,"raw_metadata":null,"created_at":"2026-07-19T02:57:44.572630Z","pmid":"41000784","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":[]}