{"doi":"10.1172/jci.insight.172959","title":"Histone demethylase JARID1C/KDM5C regulates Th17 cells by increasing IL-6 expression in diabetic plasmacytoid dendritic cells","abstract":"Plasmacytoid dendritic cells (pDCs) are first responders to tissue injury, where they prime naive T cells. The role of pDCs in physiologic wound repair has been examined, but little is known about pDCs in diabetic wound tissue and their interactions with naive CD4+ T cells. Diabetic wounds are characterized by increased levels of inflammatory IL-17A cytokine, partly due to increased Th17 CD4+ cells. This increased IL-17A cytokine, in excess, impairs tissue repair. Here, using human tissue and murine wound healing models, we found that diabetic wound pDCs produced excess IL-6 and TGF-β and that these cytokines skewed naive CD4+ T cells toward a Th17 inflammatory phenotype following cutaneous injury. Further, we identified that increased IL-6 cytokine production by diabetic wound pDCs is regulated by a histone demethylase, Jumonji AT-rich interactive domain 1C histone demethylase (JARID1C). Decreased JARID1C increased IL-6 transcription in diabetic pDCs, and this process was regulated upstream by an IFN-I/TYK2/JAK1,3 signaling pathway. When inhibited in nondiabetic wound pDCs, JARID1C skewed naive CD4+ T cells toward a Th17 phenotype and increased IL-17A production. Together, this suggests that diabetic wound pDCs are epigenetically altered to increase IL-6 expression that then affects T cell phenotype. These findings identify a therapeutically manipulable pathway in diabetic wounds.","journal":"JCI Insight","year":2024,"id":431670,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9427,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295108,"name":"Sonya Wolf","orcid":"0000-0003-3626-9274","position":1,"is_corresponding":false},{"id":295106,"name":"Amrita Joshi","orcid":"0000-0001-6936-7132","position":2,"is_corresponding":false},{"id":845856,"name":"Jadie Y. Moon","orcid":"0000-0001-9451-6806","position":3,"is_corresponding":false},{"id":295111,"name":"William J. Melvin","orcid":"0000-0002-3241-5919","position":4,"is_corresponding":false},{"id":426357,"name":"Sriganesh Sharma","orcid":"0000-0003-3551-2578","position":5,"is_corresponding":false},{"id":1236366,"name":"Frank M Davis","orcid":null,"position":6,"is_corresponding":false},{"id":340685,"name":"Andrea T. Obi","orcid":null,"position":7,"is_corresponding":false},{"id":846996,"name":"Rachel Wasikowski","orcid":null,"position":8,"is_corresponding":false},{"id":12819,"name":"Lam C. Tsoi","orcid":"0000-0003-1627-5722","position":9,"is_corresponding":false},{"id":1221325,"name":"Emily C. Barrett","orcid":null,"position":10,"is_corresponding":false},{"id":1236367,"name":"Kevin D Mangum","orcid":null,"position":11,"is_corresponding":false},{"id":228249,"name":"Tyler M. Bauer","orcid":"0000-0002-5430-5104","position":12,"is_corresponding":false},{"id":295113,"name":"Steven L. Kunkel","orcid":"0000-0002-5738-6341","position":13,"is_corresponding":false},{"id":277952,"name":"Bethany B. Moore","orcid":"0000-0003-3051-745X","position":14,"is_corresponding":false},{"id":1236368,"name":"Katherine A Gallagher","orcid":null,"position":15,"is_corresponding":false},{"id":295112,"name":"Christopher O. Audu","orcid":"0000-0002-4183-8825","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T01:59:30.747263Z","pmid":"38912581","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":[]}