{"doi":"10.4049/immunohorizons.2300039","title":"Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2","abstract":"IL-35 is an immunosuppressive cytokine with roles in cancer, autoimmunity, and infectious disease. In the conventional model of IL-35 biology, the p35 and Ebi3 domains of this cytokine interact with IL-12Rβ2 and gp130, respectively, on the cell surface of regulatory T and regulatory B cells, triggering their suppression of Th cell activity. Here we use a human IL-12 bioactivity reporter cell line, protein binding assays, and primary human Th cells to demonstrate an additional mechanism by which IL-35 suppresses Th cell activity, wherein IL-35 directly inhibits the association of IL-12 with its surface receptor IL-12Rβ2 and downstream IL-12-dependent activities. IL-12 binding to the surface receptor IL-12Rβ1 was unaffected by IL-35. These data demonstrate that in addition to acting via regulatory T and regulatory B cells, human IL-35 can also directly suppress IL-12 bioactivity and its interaction with IL-12Rβ2.","journal":"ImmunoHorizons","year":2023,"id":359465,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":915057,"name":"Marlena R. Merling","orcid":null,"position":1,"is_corresponding":false},{"id":587791,"name":"Tiffany A. Claeys","orcid":null,"position":2,"is_corresponding":false},{"id":1007642,"name":"Jack W. Dowling","orcid":"0000-0002-7435-3277","position":3,"is_corresponding":false},{"id":335063,"name":"Adriana Forero","orcid":"0000-0002-2698-658X","position":4,"is_corresponding":false},{"id":241041,"name":"Richard Robinson","orcid":"0000-0002-4699-515X","position":5,"is_corresponding":false},{"id":807367,"name":"Najmus Mahfooz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:13:52.889556Z","pmid":"37289499","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":[]}