{"doi":"10.1016/j.celrep.2023.112106","title":"DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development","abstract":"Drak2 -deficient ( Drak2 −/− ) mice are resistant to multiple models of autoimmunity yet effectively eliminate pathogens and tumors. Thus, DRAK2 represents a potential target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved. Here, we demonstrate that resistance to T1D in non-obese diabetic ( NOD ) mice is due to the absence of Drak2 in T cells and requires the presence of regulatory T cells (T regs ). Contrary to previous hypotheses, we show that DRAK2 does not limit TCR signaling. Rather, DRAK2 regulates IL-2 signaling by inhibiting STAT5A phosphorylation. We further demonstrate that enhanced sensitivity to IL-2 in the absence of Drak2 augments thymic T reg development. Overall, our data indicate that DRAK2 contributes to autoimmunity in multiple ways by regulating thymic T reg development and by impacting the sensitivity of conventional T cells to T reg -mediated suppression.","journal":"Cell Reports","year":2023,"id":345657,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"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":586264,"name":"Tarsha Harris","orcid":null,"position":1,"is_corresponding":false},{"id":1086097,"name":"Blaine Creasy","orcid":null,"position":2,"is_corresponding":false},{"id":1085631,"name":"Marie Wehenkel","orcid":"0000-0002-8103-221X","position":3,"is_corresponding":false},{"id":1085632,"name":"Marygrace Duggar","orcid":"0000-0003-1912-3302","position":4,"is_corresponding":false},{"id":298292,"name":"Benjamin A. Wilander","orcid":"0000-0001-8413-9189","position":5,"is_corresponding":false},{"id":623131,"name":"Ashutosh Mishra","orcid":"0000-0002-0953-969X","position":6,"is_corresponding":false},{"id":225728,"name":"Jeremy Chase Crawford","orcid":"0000-0003-4096-6048","position":7,"is_corresponding":false},{"id":1085633,"name":"Sarah A. Mullen","orcid":"0000-0002-7598-0985","position":8,"is_corresponding":false},{"id":1086098,"name":"Katherine M. Williams","orcid":null,"position":9,"is_corresponding":false},{"id":1085634,"name":"M. R. A. Pillai","orcid":"0000-0002-7944-3642","position":10,"is_corresponding":false},{"id":97164,"name":"Anthony A. High","orcid":"0000-0003-2323-5649","position":11,"is_corresponding":false},{"id":271011,"name":"Maureen A. McGargill","orcid":"0000-0002-0916-0372","position":12,"is_corresponding":false},{"id":1085630,"name":"Alexandra H. Mandarano","orcid":"0000-0001-7549-5317","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:11:44.152490Z","pmid":"36773294","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":[]}