{"doi":"10.4049/jimmunol.2300402","title":"Cutting Edge: STAT4 Promotes <i>Bhlhe40</i> Induction to Drive Protective IFN-γ from NK Cells during Viral Infection","abstract":"NK cells represent a cellular component of the mammalian innate immune system, and they mount rapid responses against viral infection, including the secretion of the potent antiviral effector cytokine IFN-γ. Following mouse CMV infection, Bhlhe40 was the most highly induced transcription factor in NK cells among the basic helix-loop-helix family. Bhlhe40 upregulation in NK cells depended upon IL-12 and IL-18 signals, with the promoter of Bhlhe40 enriched for STAT4 and the permissive histone H3K4me3, and with STAT4-deficient NK cells showing an impairment of Bhlhe40 induction and diminished H3K4me3. Transcriptomic and protein analysis of Bhlhe40-deficient NK cells revealed a defect in IFN-γ production during mouse CMV infection, resulting in diminished protective immunity following viral challenge. Finally, we provide evidence that Bhlhe40 directly promotes IFN-γ by binding throughout the Ifng loci in activated NK cells. Thus, our study reveals how STAT4-mediated control of Bhlhe40 drives protective IFN-γ secretion by NK cells during viral infection.","journal":"The Journal of Immunology","year":2023,"id":371737,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"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":636683,"name":"Aamna Abbasi","orcid":"0000-0002-9323-0176","position":1,"is_corresponding":false},{"id":346315,"name":"Jessica Sharrock","orcid":null,"position":2,"is_corresponding":false},{"id":636461,"name":"Endi K. Santosa","orcid":"0000-0001-9483-8354","position":3,"is_corresponding":false},{"id":469065,"name":"Sam Sheppard","orcid":"0000-0002-1420-6910","position":4,"is_corresponding":false},{"id":322860,"name":"Colleen M. Lau","orcid":"0000-0001-7538-094X","position":5,"is_corresponding":false},{"id":278786,"name":"Brian T. Edelson","orcid":"0000-0003-2856-7650","position":6,"is_corresponding":false},{"id":61584,"name":"Joseph C. Sun","orcid":"0000-0001-8062-9033","position":7,"is_corresponding":false},{"id":636463,"name":"Hyunu Kim","orcid":"0000-0001-6452-8152","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:15:49.453761Z","pmid":"37830760","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":[]}