{"doi":"10.1172/jci140508","title":"Wnt activation promotes memory T cell polyfunctionality via epigenetic regulator PRMT1","abstract":"T cell polyfunctionality is a hallmark of protective immunity against pathogens and cancer, yet the molecular mechanism governing it remains mostly elusive. We found that canonical Wnt agonists inhibited human memory CD8+ T cell differentiation while simultaneously promoting the generation of highly polyfunctional cells. Downstream effects of Wnt activation persisted after removal of the drug, and T cells remained polyfunctional following subsequent cell division, indicating the effect is epigenetically regulated. Wnt activation induced a gene expression pattern that is enriched with stem cell-specific gene signatures and upregulation of protein arginine methyltransferase 1 (PRMT1), a known epigenetic regulator. PRMT1+CD8+ T cells are associated with enhanced polyfunctionality, especially the ability to produce IL-2. In contrast, inhibition of PRMT1 ameliorated the effects of Wnt on polyfunctionality. Chromatin immunoprecipitation revealed that H4R3me2a, a permissive transcription marker mediated by PRMT1, increased at the IL-2 promoter loci following Wnt activation. In vivo, Wnt-treated T cells exhibited superior polyfunctionality and persistence. When applied to cytomegalovirus (CMV) donor-seropositive, recipient-seronegative patients (D+/R-) lung transplant patient samples, Wnt activation enhanced CMV-specific T cell polyfunctionality, which is important in controlling CMV diseases. These findings reveal a molecular mechanism governing T cell polyfunctionality and identify PRMT1 as a potential target for T cell immunotherapy.","journal":"Journal of Clinical Investigation","year":2022,"id":242767,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":757860,"name":"Yi-Hsin Lin","orcid":null,"position":1,"is_corresponding":false},{"id":873930,"name":"Qiongman Kong","orcid":"0009-0006-0314-5960","position":2,"is_corresponding":false},{"id":381898,"name":"Pali D. Shah","orcid":null,"position":3,"is_corresponding":false},{"id":873931,"name":"Joan Glick Bieler","orcid":"0000-0002-7667-1965","position":4,"is_corresponding":false},{"id":278245,"name":"Scott M. Palmer","orcid":"0000-0002-1370-3771","position":5,"is_corresponding":false},{"id":476632,"name":"Kent J. Weinhold","orcid":"0000-0003-4876-6737","position":6,"is_corresponding":false},{"id":874484,"name":"Hong-Ru Chang","orcid":null,"position":7,"is_corresponding":false},{"id":51739,"name":"Hailiang Huang","orcid":"0000-0003-1461-5762","position":8,"is_corresponding":false},{"id":275256,"name":"Robin K. Avery","orcid":"0000-0001-7692-3619","position":9,"is_corresponding":false},{"id":298449,"name":"Jonathan P. Schneck","orcid":"0000-0001-5346-2776","position":10,"is_corresponding":false},{"id":613777,"name":"Yen‐Ling Chiu","orcid":"0000-0003-4504-5571","position":11,"is_corresponding":false},{"id":873929,"name":"Bo-Yi Sung","orcid":"0000-0002-3854-4885","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:23:10.218426Z","pmid":"35040433","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":[]}