{"doi":"10.4049/jimmunol.2400331","title":"IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation","abstract":"Expression of IL-15 on the surface of human graft endothelial cells (ECs) bound to the IL-15Rα subunit can increase the activation of CTLs, potentiating allograft rejection. Our previous work showed that surface expression of this protein complex could be induced by alloantibody-mediated complement activation through increased IL-1β synthesis, secretion, and autocrine/paracrine IL-1-mediated activation of NF-κB. In this article, we report that cultured human ECs express eight differently spliced IL-15 transcripts. Remarkably, IL-1β does not alter the expression level of any IL-15 transcript but induces surface expression independently of RNA polymerase II-mediated transcription while requiring new protein translation. Mechanistically, IL-1β causes an NF-κB-mediated reduction in the level of microRNA Let-7c-3p, thereby relieving a block of translation of IL-15 surface protein. Let7c-3p anti-miR can induce EC surface expression of IL-15/IL-15Rα in the absence of complement activation or of IL-1, enabling IL-15 transpresentation to boost CD8 T cell activation. Because of the complexity we have uncovered in IL-15 regulation, we recommend caution in interpreting increased total IL-15 mRNA or protein levels as a surrogate for transpresentation.","journal":"The Journal of Immunology","year":2024,"id":450668,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":815611,"name":"Luanna Summer","orcid":"0009-0006-5188-9649","position":1,"is_corresponding":false},{"id":36521,"name":"Francesc López‐Giráldez","orcid":"0000-0001-7476-9822","position":2,"is_corresponding":false},{"id":248224,"name":"Zuzana Tobiásová","orcid":null,"position":3,"is_corresponding":false},{"id":902474,"name":"Thomas D. Manes","orcid":null,"position":4,"is_corresponding":false},{"id":1271641,"name":"Shruthi Yasothan","orcid":null,"position":5,"is_corresponding":false},{"id":913386,"name":"Guiyu Song","orcid":"0000-0003-2617-9857","position":6,"is_corresponding":false},{"id":243204,"name":"Dan Jane‐wit","orcid":"0000-0001-7115-0362","position":7,"is_corresponding":false},{"id":243179,"name":"W. Mark Saltzman","orcid":"0000-0002-2163-549X","position":8,"is_corresponding":false},{"id":243205,"name":"Jordan S. Pober","orcid":"0000-0001-5990-1071","position":9,"is_corresponding":false},{"id":409415,"name":"Clancy W. Mullan","orcid":"0000-0002-2774-251X","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:02:28.969209Z","pmid":"39302113","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":[]}