{"doi":"10.1016/j.celrep.2025.116600","title":"Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus","abstract":"Systemic lupus erythematosus (SLE) is an autoimmune disease in which the production of pathogenic autoantibodies depends on T follicular helper (T FH ) cells. This study investigated the mechanisms by which the glycolysis inhibitor 2-deoxy- d -glucose (2DG) reduces the expansion of T FH cells and the associated production of autoantibodies in lupus-prone mice. Integrated cellular, transcriptomic, epigenetic, and metabolic analyses showed that 2DG reversed the enhanced cell expansion and effector functions, as well as mitochondrial and lysosomal defects in lupus T FH cells, including increased expression of chaperone-mediated autophagy (CMA) markers associated with Toll-like receptor 7 activation. Importantly, adoptive transfer of 2DG-reprogrammed T FH cells protected lupus-prone mice from disease progression. The orthologs of genes responsive to 2DG in murine lupus T FH cells were overexpressed in the T FH cells of SLE patients, suggesting a therapeutic potential for targeting glycolysis to eliminate aberrant T FH cells and curb the production of autoantibodies that induce tissue damage.","journal":"Cell Reports","year":2025,"id":524901,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":617296,"name":"Yong Ge","orcid":null,"position":1,"is_corresponding":false},{"id":770220,"name":"Ahmed S. Elshikha","orcid":"0000-0003-3759-6832","position":2,"is_corresponding":false},{"id":863477,"name":"Yuk Pheel Park","orcid":"0000-0001-9749-5983","position":3,"is_corresponding":false},{"id":458198,"name":"Cenxiao Fang","orcid":null,"position":4,"is_corresponding":false},{"id":1399642,"name":"Milind V. Joshi","orcid":null,"position":5,"is_corresponding":false},{"id":1399643,"name":"Maria Montes de Oca Arena","orcid":null,"position":6,"is_corresponding":false},{"id":1399644,"name":"Lauren Padilla","orcid":null,"position":7,"is_corresponding":false},{"id":245745,"name":"Yanan Zhu","orcid":"0000-0003-1025-7929","position":8,"is_corresponding":false},{"id":290030,"name":"William L. Clapp","orcid":"0000-0001-5903-7113","position":9,"is_corresponding":false},{"id":608002,"name":"Eric S. Sobel","orcid":"0000-0003-3048-0589","position":10,"is_corresponding":false},{"id":616023,"name":"Mansour Mohamadzadeh","orcid":"0000-0002-7356-7724","position":11,"is_corresponding":false},{"id":302973,"name":"Laurence Morel","orcid":"0000-0002-6622-1290","position":12,"is_corresponding":false},{"id":1340236,"name":"Seung Chul Choi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41275496","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":[]}