{"doi":"10.3389/fphys.2021.688485","title":"Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function","abstract":"Lactate and the associated H + ions are still introduced in many biochemistry and general biology textbooks and courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, the role of lactate as a fuel source has been well-appreciated in the field of physiology, and the role of lactate as a metabolic feedback regulator and distinct signaling molecule is beginning to gain traction in the field of immunology. We now know that while lactate and the associated H + ions are generally immunosuppressive negative regulators, there are cell, receptor, mediator, and microenvironment-specific effects that augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, and neutrophil functions. Moreover, we are beginning to uncover how lactate and H + utilize different transporters and signaling cascades in various immune cell types. These immunomodulatory effects may have a substantial impact in cancer, sepsis, autoimmunity, wound healing, and other immunomodulatory conditions with elevated lactate levels. In this article, we summarize the known effects of lactate and H + on immune cells to hypothesize potential explanations for the divergent inflammatory vs. anti-inflammatory effects.","journal":"Frontiers in Physiology","year":2021,"id":147077,"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":177,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407049,"name":"Daniel Abebayehu","orcid":"0000-0002-6837-3028","position":1,"is_corresponding":false},{"id":564498,"name":"Julia A. Pinette","orcid":"0000-0003-0715-7708","position":2,"is_corresponding":false},{"id":384854,"name":"John Ryan","orcid":"0000-0002-9203-5512","position":3,"is_corresponding":false},{"id":450965,"name":"Heather L. Caslin","orcid":"0000-0002-7471-6779","position":0,"is_corresponding":true}],"reference_count":154,"raw_metadata":null,"created_at":"2026-07-18T23:42:30.206628Z","pmid":"34733170","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":[]}