{"doi":"10.1016/j.celrep.2023.112996","title":"IL-2 can signal via chemokine receptors to promote regulatory T cells’ suppressive function","abstract":"Canonical interleukin-2 (IL-2) signaling via the high-affinity CD25-containing IL-2 receptor-Janus kinase (JAK)1,3-signal transducer and activator of transcription 5 (STAT5) pathway is essential for development and maintenance of CD4 + CD25 Hi Foxp3 + regulatory T cells (Tregs) that support immune homeostasis. Here, we report that IL-2 signaling via an alternative CD25-chemokine receptor pathway promotes the suppressive function of Tregs. Using an antibody against CD25 that biases IL-2 signaling toward this alternative pathway, we establish that this pathway increases the suppressive activity of Tregs and ameliorates murine experimental autoimmune encephalomyelitis (EAE). Furthermore, heparan sulfate, an IL-2-binding element of cell surfaces and extracellular matrix, or an engineered IL-2 immunocytokine can also direct IL-2 signaling toward this alternative pathway. Overall, these data reveal a non-canonical mechanism for IL-2 signaling that promotes suppressive functions of Tregs, further elucidates how IL-2 supports immune homeostasis, and suggests approaches to promote or suppress Treg functions.","journal":"Cell Reports","year":2023,"id":325143,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":1042597,"name":"Ho Sup Lee","orcid":"0000-0001-5974-6884","position":1,"is_corresponding":false},{"id":1043330,"name":"S H Kim","orcid":null,"position":2,"is_corresponding":false},{"id":1043331,"name":"Mikhael Fernandes de Lima","orcid":null,"position":3,"is_corresponding":false},{"id":288435,"name":"Alexandre R. Gingras","orcid":"0000-0002-5373-0176","position":4,"is_corresponding":false},{"id":830501,"name":"Qinyi Du","orcid":null,"position":5,"is_corresponding":false},{"id":1043332,"name":"Wilma McLaughlin","orcid":null,"position":6,"is_corresponding":false},{"id":1043333,"name":"Jailail Ablack","orcid":null,"position":7,"is_corresponding":false},{"id":288439,"name":"Miguel Alejandro Lopez‐Ramirez","orcid":"0000-0001-7089-4060","position":8,"is_corresponding":false},{"id":288433,"name":"Frédéric Lagarrigue","orcid":"0000-0002-4660-8666","position":9,"is_corresponding":false},{"id":324388,"name":"Zhichao Fan","orcid":"0000-0001-5385-9626","position":10,"is_corresponding":false},{"id":225253,"name":"John T. Chang","orcid":"0000-0003-0873-6218","position":11,"is_corresponding":false},{"id":868916,"name":"Derek VanDyke","orcid":"0000-0002-0494-7184","position":12,"is_corresponding":false},{"id":530310,"name":"Jamie B. Spangler","orcid":"0000-0001-8187-3732","position":13,"is_corresponding":false},{"id":288441,"name":"Mark H. Ginsberg","orcid":"0000-0002-5685-5417","position":14,"is_corresponding":false},{"id":288436,"name":"Hao Sun","orcid":"0000-0002-4790-8847","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:08:22.919783Z","pmid":"37598341","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":[]}