{"doi":"10.1172/jci.insight.136437","title":"Metabolic reprogramming augments potency of human pSTAT3–inhibited iTregs to suppress alloreactivity","abstract":"Immunosuppressive donor Tregs can prevent graft-versus-host disease (GVHD) or solid-organ allograft rejection. We previously demonstrated that inhibiting STAT3 phosphorylation (pSTAT3) augments FOXP3 expression, stabilizing induced Tregs (iTregs). Here we report that human pSTAT3-inhibited iTregs prevent human skin graft rejection and xenogeneic GVHD yet spare donor antileukemia immunity. pSTAT3-inhibited iTregs express increased levels of skin-homing cutaneous lymphocyte-associated antigen, immunosuppressive GARP and PD-1, and IL-9 that supports tolerizing mast cells. Further, pSTAT3-inhibited iTregs significantly reduced alloreactive conventional T cells, Th1, and Th17 cells implicated in GVHD and tissue rejection and impaired infiltration by pathogenic Th2 cells. Mechanistically, pSTAT3 inhibition of iTregs provoked a shift in metabolism from oxidative phosphorylation (OxPhos) to glycolysis and reduced electron transport chain activity. Strikingly, cotreatment with coenzyme Q10 restored OxPhos in pSTAT3-inhibited iTregs and augmented their suppressive potency. These findings support the rationale for clinically testing the safety and efficacy of metabolically tuned, human pSTAT3-inhibited iTregs to control alloreactive T cells.","journal":"JCI Insight","year":2020,"id":79338,"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":0.9461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":356122,"name":"Mario R. Fernandez","orcid":"0000-0002-2017-9576","position":1,"is_corresponding":false},{"id":412069,"name":"Elizabeth M. Sagatys","orcid":"0000-0002-4208-1916","position":2,"is_corresponding":false},{"id":412913,"name":"Jordan Reff","orcid":null,"position":3,"is_corresponding":false},{"id":332433,"name":"Jongphil Kim","orcid":"0000-0002-7430-2226","position":4,"is_corresponding":false},{"id":412070,"name":"Marie Catherine Lee","orcid":"0000-0002-1756-7279","position":5,"is_corresponding":false},{"id":412071,"name":"John V. Kiluk","orcid":"0000-0001-5889-2441","position":6,"is_corresponding":false},{"id":242418,"name":"Jane Yuet Ching Hui","orcid":"0000-0002-2628-0720","position":7,"is_corresponding":false},{"id":412072,"name":"David H. McKenna","orcid":"0000-0001-8734-0996","position":8,"is_corresponding":false},{"id":412073,"name":"Meghan Hupp","orcid":"0000-0002-2861-7585","position":9,"is_corresponding":false},{"id":412074,"name":"Colleen L. Forster","orcid":"0000-0001-5593-882X","position":10,"is_corresponding":false},{"id":331506,"name":"Michael A. Linden","orcid":"0000-0002-7433-1676","position":11,"is_corresponding":false},{"id":362036,"name":"Nicholas J. Lawrence","orcid":"0000-0003-1129-2558","position":12,"is_corresponding":false},{"id":362037,"name":"Harshani R. Lawrence","orcid":"0000-0002-9263-7775","position":13,"is_corresponding":false},{"id":315794,"name":"Joseph Pidala","orcid":null,"position":14,"is_corresponding":false},{"id":313707,"name":"Steven Z. Pavletic","orcid":"0000-0001-9111-9354","position":15,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":16,"is_corresponding":false},{"id":412075,"name":"Saı̈d M. Sebti","orcid":"0000-0001-5163-1038","position":17,"is_corresponding":false},{"id":226779,"name":"John L. Cleveland","orcid":"0000-0002-7561-9065","position":18,"is_corresponding":false},{"id":412076,"name":"Claudio Anasetti","orcid":"0000-0002-0119-0622","position":19,"is_corresponding":false},{"id":196669,"name":"B Betts","orcid":"0000-0001-7643-2422","position":20,"is_corresponding":false},{"id":412068,"name":"Kelly Walton","orcid":"0000-0001-9780-9401","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T21:50:33.748601Z","pmid":"32255769","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":[]}