{"doi":"10.17615/mcsw-pv55","title":"-Cell-Specific IL-2 Therapy Increases Islet Foxp3+Treg and Suppresses Type 1 Diabetes in NOD Mice","abstract":"Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of forkhead box p3–expressing regulatory T cells (Foxp3+Tregs). Dysregulation of the IL-2–IL-2 receptor axis is associated with aberrant Foxp3+Tregs and T cell–mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant IL-2 has been reported to enhance Foxp3+Tregs and suppress different models of autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving sufficient levels of IL-2 to boost tissue-resident Foxp3+Tregs while avoiding the potential toxic effects of systemic IL-2. With this in mind, adeno-associated virus (AAV) vector gene delivery was used to localize IL-2 expression to the islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2 driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3+Tregs in the islets but not the draining pancreatic lymph nodes. Islet Foxp3+Tregs in dsAAVmIP-IL2–treated NOD mice exhibited enhanced fitness marked by increased expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic IL-2 had no significant effect on conventional islet-infiltrating effector T cells. Notably, β-cell–specific IL-2 expression suppressed late preclinical type 1 diabetes in NOD mice. Collectively, these findings demonstrate that β-cell–specific IL-2 expands an islet-resident Foxp3+Tregs pool that effectively suppresses ongoing type 1 diabetes long term.","journal":"UNC Libraries","year":2020,"id":142373,"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":0.9412,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":540417,"name":"R. Tisch","orcid":null,"position":1,"is_corresponding":false},{"id":416727,"name":"R. J. Samulski","orcid":null,"position":2,"is_corresponding":false},{"id":609465,"name":"M. C. Johnson","orcid":null,"position":3,"is_corresponding":false},{"id":596602,"name":"CHRIS LI","orcid":null,"position":4,"is_corresponding":false},{"id":533947,"name":"A. L. Garland","orcid":null,"position":5,"is_corresponding":false},{"id":166853,"name":"B. Wang","orcid":null,"position":6,"is_corresponding":false},{"id":544925,"name":"S. C. Nicolson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:31.424593Z","pmid":null,"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":[]}