{"doi":"10.1101/2023.02.26.529772","title":"FOXP3 <sup>+</sup> regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues","abstract":"Abstract FOXP3 + regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resource in vivo . Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE -/- Treg have impaired stability and function in vivo , including the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their tolerogenic function in vivo . Together, these data identify novel roles for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity. One-Sentence Summary Regulatory T cells use heparanase to strip IL-2 bound to extracellular matrix within inflamed tissues, thereby supporting their homeostasis and function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395898,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"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":720838,"name":"Ievgen Koliesnik","orcid":"0000-0003-1959-7954","position":1,"is_corresponding":false},{"id":381353,"name":"Gernot Kaber","orcid":"0000-0002-6184-5192","position":2,"is_corresponding":false},{"id":1171660,"name":"Jacqueline Kelsey Reid","orcid":null,"position":3,"is_corresponding":false},{"id":381352,"name":"Nadine Nagy","orcid":"0000-0002-2638-2436","position":4,"is_corresponding":false},{"id":107281,"name":"Graham L. Barlow","orcid":"0000-0001-9335-5414","position":5,"is_corresponding":false},{"id":759006,"name":"Ben Falk","orcid":null,"position":6,"is_corresponding":false},{"id":1171356,"name":"Carlos Medina","orcid":"0000-0002-8324-7994","position":7,"is_corresponding":false},{"id":382285,"name":"Aviv Hargil","orcid":null,"position":8,"is_corresponding":false},{"id":298155,"name":"Israël Vlodavsky","orcid":"0000-0001-9921-898X","position":9,"is_corresponding":false},{"id":491632,"name":"Jin‐Ping Li","orcid":"0000-0002-4255-3581","position":10,"is_corresponding":false},{"id":946040,"name":"Magdiel Pérez-Cruz","orcid":"0000-0003-1215-2100","position":11,"is_corresponding":false},{"id":291711,"name":"Sai-Wen Tang","orcid":"0000-0001-8577-2461","position":12,"is_corresponding":false},{"id":381361,"name":"Everett Meyer","orcid":"0000-0001-7953-853X","position":13,"is_corresponding":false},{"id":1171357,"name":"Lucile E. 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Martinez","orcid":"0000-0003-1129-3382","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:19:27.044553Z","pmid":"36909599","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":[]}