{"doi":"10.1084/jem.20011128","title":"Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression","abstract":"<jats:p>Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system–restricted interferon regulatory factor that is required for lymphocyte activation, but its molecular functions in the T lineage remain to be elucidated. We demonstrate that IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven transcriptional activation of the IL-4 promoter. This function is dependent on the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the IL-4–inducing transcription factor, c-maf, to augment IL-4 promoter activity as well as to elicit significant levels of endogenous IL-4 production. Furthermore, naïve T helper cells from mice lacking IRF4 are compromised severely for the production of IL-4 and other Th2 cytokines. The identification of IRF4 as a partner for NFATc2 in IL-4 gene regulation provides an important molecular function for IRF4 in T helper cell differentiation.</jats:p>","journal":"The Journal of Experimental Medicine","year":2002,"id":616402,"datarank":0.8462860606407172,"base_score":5.641907070938114,"endowment":5.641907070938114,"self_citation_contribution":0.8462860606407172,"citation_network_contribution":0.0,"self_endowment_contribution":0.8462860606407172,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":281,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1589151,"name":"Kerri A. Mowen","orcid":null,"position":1,"is_corresponding":false},{"id":1589153,"name":"Kathryn D. McBride","orcid":null,"position":2,"is_corresponding":false},{"id":1051917,"name":"Erica D. Smith","orcid":"0000-0002-5424-580X","position":3,"is_corresponding":false},{"id":493782,"name":"Harinder Singh","orcid":"0000-0002-0160-1575","position":4,"is_corresponding":false},{"id":34478,"name":"Laurie H. Glimcher","orcid":"0000-0002-4971-0404","position":5,"is_corresponding":false},{"id":280891,"name":"Jyothi Rengarajan","orcid":"0000-0003-1241-4705","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression.","abstract":"Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system-restricted interferon regulatory factor that is required for lymphocyte activation, but its molecular functions in the T lineage remain to be elucidated. We demonstrate that IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven transcriptional activation of the IL-4 promoter. This function is dependent on the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the IL-4-inducing transcription factor, c-maf, to augment IL-4 promoter activity as well as to elicit significant levels of endogenous IL-4 production. Furthermore, naïve T helper cells from mice lacking IRF4 are compromised severely for the production of IL-4 and other Th2 cytokines. The identification of IRF4 as a partner for NFATc2 in IL-4 gene regulation provides an important molecular function for IRF4 in T helper cell differentiation.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11956291","pmcid":"PMC2193700","openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jem/article-pdf/195/8/1003/1139080/jem19581003.pdf","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2193700","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2193700","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2193700?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Th2 Cells","Cell Line, Transformed","Tumor Cells, Cultured","Animals","Mice, Inbred C57BL","Mice, Knockout","Humans","Mice","DNA-Binding Proteins","Proto-Oncogene Proteins","Nuclear Proteins","Transcription Factors","Interleukin-4","Cell Differentiation","Binding Sites","NFATC Transcription Factors","Interferon Regulatory Factors","Proto-Oncogene Proteins c-maf","Promoter Regions, Genetic","Transcriptional Activation","Interferon Regulatory Factor-4"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T22:48:06.492612Z","pmid":null,"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":[]}