{"doi":"10.1101/2023.12.01.569613","title":"An IL-2 mutein increases IL-10 and CTLA-4-dependent suppression of dendritic cells by regulatory T cells","abstract":"Summary Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3 + regulatory T (T R ) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated T R population with elevated proliferation, a transcriptional program associated with Stat5- and TCR-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface MHC class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 costimulatory ligands from maturing cDCs to T R cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes resulting in T cell anergy. Thus, IL-2 mutein-expanded T R cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":414620,"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":0.9575,"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":330055,"name":"Matthew Lawrance","orcid":null,"position":1,"is_corresponding":false},{"id":1196582,"name":"Chun Jing Wang","orcid":null,"position":2,"is_corresponding":false},{"id":432351,"name":"Hannah A. DeBerg","orcid":"0000-0002-5263-158X","position":3,"is_corresponding":false},{"id":126454,"name":"D M Sansom","orcid":"0000-0001-6506-3115","position":4,"is_corresponding":false},{"id":438184,"name":"Marc A. Gavin","orcid":"0000-0003-3077-1319","position":5,"is_corresponding":false},{"id":1015035,"name":"Lucy S. K. Walker","orcid":"0000-0001-5986-5015","position":6,"is_corresponding":false},{"id":108917,"name":"Daniel Campbell","orcid":"0000-0002-9652-7178","position":7,"is_corresponding":false},{"id":1196243,"name":"Braxton L. Jamison","orcid":"0000-0001-7392-929X","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T01:22:05.177070Z","pmid":"38106196","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":[]}