{"doi":"10.3389/fimmu.2022.839390","title":"Alcohol Impairs Immunometabolism and Promotes Naïve T Cell Differentiation to Pro-Inflammatory Th1 CD4+ T Cells","abstract":"CD4 + T cell differentiation to pro-inflammatory and immunosuppressive subsets depends on immunometabolism. Pro-inflammatory CD4 + subsets rely on glycolysis, while immunosuppressive Treg cells require functional mitochondria for their differentiation and function. Previous pre-clinical studies have shown that ethanol (EtOH) administration increases pro-inflammatory CD4 + T cell subsets; whether this shift in immunophenotype is linked to alterations in CD4 + T cell metabolism had not been previously examined. The objective of this study was to determine whether ethanol alters CD4 + immunometabolism, and whether this affects CD4 + T cell differentiation. Naïve human CD4 + T cells were plated on anti-CD3 coated plates with soluble anti-CD28, and differentiated with IL-12 in the presence of ethanol (0 and 50 mM) for 3 days. Both Tbet-expressing (Th1) and FOXP3-expressing (Treg) CD4 + T cells increased after differentiation. Ethanol dysregulated CD4 + T cell differentiation by increasing Th1 and decreasing Treg CD4 + T cell subsets. Ethanol increased glycolysis and impaired oxidative phosphorylation in differentiated CD4 + T cells. Moreover, the glycolytic inhibitor 2-deoxyglucose (2-DG) prevented the ethanol-mediated increase in Tbet-expressing CD4 + T cells but did not attenuate the decrease in FOXP3 expression in differentiated CD4 + T cells. Ethanol increased Treg mitochondrial volume and altered expression of genes implicated in mitophagy and autophagosome formation ( PINK1 and ATG7) . These results suggest that ethanol impairs CD4 + T cell immunometabolism and disrupts mitochondrial repair processes as it promotes CD4 + T cell differentiation to a pro-inflammatory phenotype.","journal":"Frontiers in Immunology","year":2022,"id":247213,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9431,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":496202,"name":"Danielle E. Levitt","orcid":"0000-0003-1865-1971","position":1,"is_corresponding":false},{"id":415283,"name":"David A. Welsh","orcid":"0000-0002-0008-6161","position":2,"is_corresponding":false},{"id":473515,"name":"Liz Simon","orcid":"0000-0003-4149-3406","position":3,"is_corresponding":false},{"id":801164,"name":"Robert W. Siggins","orcid":"0000-0003-3380-9458","position":4,"is_corresponding":false},{"id":374494,"name":"Patricia E. Molina","orcid":"0000-0002-3598-384X","position":5,"is_corresponding":false},{"id":801163,"name":"Patrick M. McTernan","orcid":"0000-0003-4857-7901","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:23:53.369530Z","pmid":"35634279","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":[]}