{"doi":"10.3390/ijms26136078","title":"Balancing Immunity: GSK-3’s Divergent Roles in Dendritic Cell-Mediated T-Cell Priming and Memory Responses","abstract":"Glycogen synthase kinase-3 (GSK-3)-particularly the GSK-3β isoform-plays a pivotal role in regulating dendritic cell (DC) functions, including maturation, cytokine production, and antigen presentation. In immature DCs, GSK-3β is continuously active, and its inhibition has been shown to enhance DC maturation and function. As a key upstream kinase of β-catenin, GSK-3 inhibition activates β-catenin in both human and murine DCs-a pathway traditionally linked to its immunomodulatory effects. However, our recent findings challenge this paradigm by uncovering β-catenin-independent, dual roles of GSK-3β in DCs. Our study reveals that while GSK-3β enhances DC-mediated cross-priming of CD8 T cells, it concurrently impairs the generation of memory CD8 T cells. These findings have significant implications for vaccine development and cancer immunotherapy, where both effective T-cell priming and durable memory responses are critical. This mini-review provides an in-depth analysis of mechanistic insights into GSK-3β's paradoxical functions and discusses potential strategies to fine-tune GSK-3 activity for optimized immunotherapeutic outcomes.","journal":"International Journal of Molecular Sciences","year":2025,"id":533982,"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":0.9506,"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":1268546,"name":"Tianle Ma","orcid":"0000-0003-2309-1489","position":1,"is_corresponding":false},{"id":334894,"name":"Li Zhou","orcid":"0000-0002-7028-3865","position":2,"is_corresponding":false},{"id":242437,"name":"Qing‐Sheng Mi","orcid":"0000-0002-1411-6827","position":3,"is_corresponding":false},{"id":259860,"name":"Aimin Jiang","orcid":"0000-0001-9161-5729","position":4,"is_corresponding":false},{"id":125730,"name":"Chunmei Fu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:51:43.451278Z","pmid":"40649856","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":[]}