{"doi":"10.1084/jem.20221757","title":"IL-6 selectively suppresses cDC1 specification via C/EBPβ","abstract":"Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPβ binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPβ induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity.","journal":"The Journal of Experimental Medicine","year":2023,"id":325471,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"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":699736,"name":"Jing Chen","orcid":"0000-0002-5998-6930","position":1,"is_corresponding":false},{"id":1043116,"name":"Suin Jo","orcid":"0000-0002-7575-9017","position":2,"is_corresponding":false},{"id":395806,"name":"Feiya Ou","orcid":"0000-0001-8289-4025","position":3,"is_corresponding":false},{"id":699735,"name":"Stephen T. Ferris","orcid":"0000-0003-3340-2607","position":4,"is_corresponding":false},{"id":299070,"name":"Tiantian Liu","orcid":"0000-0001-9377-9938","position":5,"is_corresponding":false},{"id":299072,"name":"Ray A. Ohara","orcid":"0000-0001-7897-3169","position":6,"is_corresponding":false},{"id":299069,"name":"David A. Anderson","orcid":"0000-0001-9286-5789","position":7,"is_corresponding":false},{"id":782545,"name":"Renee Wu","orcid":"0000-0002-9521-1657","position":8,"is_corresponding":false},{"id":1043117,"name":"M. Chen","orcid":"0000-0002-7820-1035","position":9,"is_corresponding":false},{"id":1043118,"name":"W.E. Gillanders","orcid":"0009-0008-7335-6039","position":10,"is_corresponding":false},{"id":235670,"name":"William E. Gillanders","orcid":"0000-0002-0465-3071","position":11,"is_corresponding":false},{"id":299074,"name":"Theresa L. Murphy","orcid":"0000-0001-6539-8142","position":12,"is_corresponding":false},{"id":227901,"name":"Kenneth M. Murphy","orcid":"0000-0002-3505-9630","position":13,"is_corresponding":false},{"id":299067,"name":"Sun Kyung Kim","orcid":"0000-0002-1375-6339","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:08:22.919783Z","pmid":"37432392","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":[]}