{"doi":"10.1016/j.celrep.2020.108500","title":"Lactate Limits T Cell Proliferation via the NAD(H) Redox State","abstract":"Immune cell function is influenced by metabolic conditions. Low-glucose, high-lactate environments, such as the placenta, gastrointestinal tract, and the tumor microenvironment, are immunosuppressive, especially for glycolysis-dependent effector T cells. We report that nicotinamide adenine dinucleotide (NAD+), which is reduced to NADH by lactate dehydrogenase in lactate-rich conditions, is a key point of metabolic control in T cells. Reduced NADH is not available for NAD+-dependent enzymatic reactions involving glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate dehydrogenase (PGDH). We show that increased lactate leads to a block at GAPDH and PGDH, leading to the depletion of post-GAPDH glycolytic intermediates, as well as the 3-phosphoglycerate derivative serine that is known to be important for T cell proliferation. Supplementing serine rescues the ability of T cells to proliferate in the presence of lactate-induced reductive stress. Directly targeting the redox state may be a useful approach for developing novel immunotherapies in cancer and therapeutic immunosuppression.","journal":"Cell Reports","year":2020,"id":48712,"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":356,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"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":231748,"name":"Jing Jiao","orcid":"0000-0002-0018-1353","position":1,"is_corresponding":false},{"id":231749,"name":"Tara TeSlaa","orcid":"0000-0002-0504-0998","position":2,"is_corresponding":false},{"id":231750,"name":"Jason Stadanlick","orcid":"0000-0003-1112-6736","position":3,"is_corresponding":false},{"id":65744,"name":"Zhong Lin Wang","orcid":"0000-0002-5530-0380","position":4,"is_corresponding":false},{"id":231751,"name":"Liqing Wang","orcid":"0000-0001-7600-6992","position":5,"is_corresponding":false},{"id":231752,"name":"Tatiana Akimova","orcid":"0000-0003-2767-8762","position":6,"is_corresponding":false},{"id":231753,"name":"Alessia Angelin","orcid":"0000-0002-7115-5451","position":7,"is_corresponding":false},{"id":231754,"name":"Patrick Schäfer","orcid":"0000-0002-0366-6858","position":8,"is_corresponding":false},{"id":231755,"name":"Michelle D. Cully","orcid":"0000-0002-3873-4929","position":9,"is_corresponding":false},{"id":231756,"name":"Caroline Perry","orcid":"0000-0002-6022-5741","position":10,"is_corresponding":false},{"id":231757,"name":"Piotr Kopiński","orcid":"0000-0003-2776-1945","position":11,"is_corresponding":false},{"id":231758,"name":"Lili Guo","orcid":"0000-0002-7036-0234","position":12,"is_corresponding":false},{"id":231759,"name":"Ian A. Blair","orcid":"0000-0003-0366-8658","position":13,"is_corresponding":false},{"id":231760,"name":"Louis R. Ghanem","orcid":"0000-0002-7723-5241","position":14,"is_corresponding":false},{"id":234237,"name":"Michael S. Leibowitz","orcid":null,"position":15,"is_corresponding":false},{"id":231761,"name":"Wayne W. Hancock","orcid":"0000-0002-7211-5291","position":16,"is_corresponding":false},{"id":231762,"name":"Edmund K. Moon","orcid":"0000-0002-5827-2768","position":17,"is_corresponding":false},{"id":231763,"name":"Matthew H. Levine","orcid":"0000-0003-4525-5827","position":18,"is_corresponding":false},{"id":231764,"name":"Evgeniy Eruslanov","orcid":"0000-0003-0743-5026","position":19,"is_corresponding":false},{"id":227783,"name":"Douglas C. Wallace","orcid":"0000-0002-7480-8278","position":20,"is_corresponding":false},{"id":231765,"name":"Joseph A. Baur","orcid":"0000-0001-8262-6549","position":21,"is_corresponding":false},{"id":231766,"name":"Ulf H. Beier","orcid":"0000-0002-3672-572X","position":22,"is_corresponding":false},{"id":231747,"name":"William J. Quinn","orcid":"0000-0002-3642-584X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T20:35:18.908826Z","pmid":"33326785","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":[]}