{"doi":"10.1016/j.celrep.2025.115775","title":"KMT2D coordinates antiviral CD4+ T cell responses through opposing effects on T follicular helper and cytotoxic gene expression","abstract":"T follicular helper (T FH ) cells are essential for protective antibody responses. Histone modifications direct T FH development and function; however, the role of specific chromatin modifiers in this process is not well understood. Lysine methyltransferase 2D (KMT2D) is a histone methyltransferase that acts at H 3 K 4 to promote gene expression. Herein, we examined the contribution of KMT2D to T cell responses during acute lymphocytic choriomeningitis virus infection. Mice lacking KMT2D in T cells generated sufficient antiviral CD8 + T cell responses to resolve infection. However, these mice formed fewer T FH cells and had diminished germinal center and antibody responses. Mechanistically, KMT2D sustained T FH responses in part by promoting Thpok and Il21 expression through H 3 K 4 Me 1 deposition at gene enhancers. Consistent with loss of THPOK, KMT2D-deficient CD4 + T cells acquired a cytotoxic CD4 + T (CD4 CTL ) cell phenotype involving elevated expression of RUNX3, EOMES, and cytolytic molecules. Our findings show KMT2D balances T FH development and humoral immunity over CD4 CTL cells.","journal":"Cell Reports","year":2025,"id":567379,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1112345,"name":"Ashlyn A. Buzzelli","orcid":"0000-0002-1704-3619","position":1,"is_corresponding":false},{"id":1084496,"name":"Gabrielle Quickstad","orcid":"0000-0003-2458-8286","position":2,"is_corresponding":false},{"id":780090,"name":"Lixin Yang","orcid":"0000-0002-7361-7584","position":3,"is_corresponding":false},{"id":603293,"name":"Ichiro Misumi","orcid":"0000-0003-3892-7605","position":4,"is_corresponding":false},{"id":347127,"name":"Karl B. Shpargel","orcid":"0000-0002-9658-456X","position":5,"is_corresponding":false},{"id":275085,"name":"Jason K. Whitmire","orcid":"0000-0003-2578-6073","position":6,"is_corresponding":false},{"id":569678,"name":"Jonathan Cohen","orcid":"0000-0002-4673-7644","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T02:56:44.340853Z","pmid":"40460200","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":[]}