{"doi":"10.4049/jimmunol.2300248","title":"SIKs Regulate HDAC7 Stabilization and Cytokine Recall in Late-Stage T Cell Effector Differentiation","abstract":"Understanding the mechanisms underlying the acquisition and maintenance of effector function during T cell differentiation is important to unraveling how these processes can be dysregulated in the context of disease and manipulated for therapeutic intervention. In this study, we report the identification of a previously unappreciated regulator of murine T cell differentiation through the evaluation of a previously unreported activity of the kinase inhibitor, BioE-1197. Specifically, we demonstrate that liver kinase B1 (LKB1)-mediated activation of salt-inducible kinases epigenetically regulates cytokine recall potential in effector CD8+ and Th1 cells. Evaluation of this phenotype revealed that salt-inducible kinase-mediated phosphorylation-dependent stabilization of histone deacetylase 7 (HDAC7) occurred during late-stage effector differentiation. HDAC7 stabilization increased nuclear HDAC7 levels, which correlated with total and cytokine loci-specific reductions in the activating transcription mark histone 3 lysine 27 acetylation (H3K27Ac). Accordingly, HDAC7 stabilization diminished transcriptional induction of cytokine genes upon restimulation. Inhibition of this pathway during differentiation produced effector T cells epigenetically poised for enhanced cytokine recall. This work identifies a previously unrecognized target for enhancing effector T cell functionality.","journal":"The Journal of Immunology","year":2023,"id":379241,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":864357,"name":"Alberto Marín-González","orcid":"0000-0002-9076-1270","position":1,"is_corresponding":false},{"id":229834,"name":"Chirag H. Patel","orcid":null,"position":2,"is_corresponding":false},{"id":228361,"name":"Im‐Hong Sun","orcid":"0000-0003-0288-2062","position":3,"is_corresponding":false},{"id":41931,"name":"Jiayu Wen","orcid":"0000-0003-1249-6456","position":4,"is_corresponding":false},{"id":655134,"name":"Robert D. Leone","orcid":"0000-0002-2983-8531","position":5,"is_corresponding":false},{"id":417268,"name":"Bridget Duvall","orcid":null,"position":6,"is_corresponding":false},{"id":745231,"name":"Run‐Duo Gao","orcid":null,"position":7,"is_corresponding":false},{"id":22168,"name":"Taekjip Ha","orcid":"0000-0003-2195-6258","position":8,"is_corresponding":false},{"id":416671,"name":"Takashi Tsukamoto","orcid":"0000-0002-0216-7520","position":9,"is_corresponding":false},{"id":228373,"name":"Barbara S. Slusher","orcid":"0000-0001-9814-4157","position":10,"is_corresponding":false},{"id":299278,"name":"Joel L. Pomerantz","orcid":"0000-0002-5030-1018","position":11,"is_corresponding":false},{"id":228375,"name":"Jonathan D. Powell","orcid":"0000-0002-0850-2852","position":12,"is_corresponding":false},{"id":1143667,"name":"Rachel Shannon Helms","orcid":"0000-0001-7126-7122","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:16:52.622552Z","pmid":"37947442","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":[]}