{"doi":"10.1101/2020.03.12.989707","title":"Glycolysis Fuels Phosphoinositide 3-Kinase Signaling to Bolster T Cell Immunity","abstract":"Abstract Infection triggers clonal expansion and effector differentiation of microbial antigen-specific T cells in association with metabolic reprograming. Here, we show that the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced in CD8 + T effector cells via phosphoinositide 3-kinase (PI3K)-dependent mechanisms. In turn, ablation of LDHA inhibits PI3K-dependent phosphorylation of Akt and its transcription factor target Foxo1, causing defective antimicrobial immunity. LDHA deficiency cripples cellular redox control and diminishes glycolytic adenosine triphosphate (ATP) production in effector T cells, resulting in attenuated PI3K signaling. Thus, nutrient metabolism and growth factor signaling are highly integrated processes with glycolytic ATP serving as a rheostat to gauge PI3K/Akt/Foxo1 signaling in T cell immunity control. Such a bioenergetics mechanism of signaling regulation implies a root cause for the century-old phenomenon of Warburg effect, and could guide development of novel therapeutics for infectious diseases and cancer. One Sentence Summary A PI3K and LDHA circuit enables T cell immunity","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119181,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"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":553658,"name":"Na Yin","orcid":"0000-0002-8280-6512","position":1,"is_corresponding":false},{"id":246220,"name":"Min Peng","orcid":"0000-0002-5885-0660","position":2,"is_corresponding":false},{"id":240582,"name":"Efstathios G. Stamatiades","orcid":"0000-0002-2785-9005","position":3,"is_corresponding":false},{"id":437328,"name":"Amy Shyu","orcid":"0000-0001-6039-0408","position":4,"is_corresponding":false},{"id":553659,"name":"Peng Li","orcid":"0000-0002-3893-076X","position":5,"is_corresponding":false},{"id":240584,"name":"Xian Zhang","orcid":"0000-0001-9674-7886","position":6,"is_corresponding":false},{"id":240580,"name":"H. Mytrang","orcid":"0000-0002-3043-3902","position":7,"is_corresponding":false},{"id":553660,"name":"Zhaoquan Wang","orcid":"0000-0001-8227-0941","position":8,"is_corresponding":false},{"id":240587,"name":"Kristelle J. Capistrano","orcid":"0000-0003-4349-9924","position":9,"is_corresponding":false},{"id":240581,"name":"Chun Chou","orcid":"0000-0001-7147-4236","position":10,"is_corresponding":false},{"id":235390,"name":"Andrew G. Levine","orcid":"0000-0003-3717-7558","position":11,"is_corresponding":false},{"id":90403,"name":"Alexander Y. Rudensky","orcid":"0000-0003-1280-2898","position":12,"is_corresponding":false},{"id":240589,"name":"Ming O. Li","orcid":"0000-0002-1383-0535","position":13,"is_corresponding":false},{"id":437327,"name":"Ke Xu","orcid":"0000-0002-6707-1052","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:14:08.313144Z","pmid":null,"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":[]}