{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:52:08Z","timestamp":1789555928607,"version":"build-2803163510"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32, P60"],"award-info":[{"award-number":["T32, P60"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation to pro-inflammatory and immunosuppressive subsets depends on immunometabolism. Pro-inflammatory CD4\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets; whether this shift in immunophenotype is linked to alterations in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell metabolism had not been previously examined. The objective of this study was to determine whether ethanol alters CD4\n                    <jats:sup>+<\/jats:sup>\n                    immunometabolism, and whether this affects CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Na\u00efve human CD4\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cells increased after differentiation. Ethanol dysregulated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation by increasing Th1 and decreasing Treg CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets. Ethanol increased glycolysis and impaired oxidative phosphorylation in differentiated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Moreover, the glycolytic inhibitor 2-deoxyglucose (2-DG) prevented the ethanol-mediated increase in Tbet-expressing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells but did not attenuate the decrease in FOXP3 expression in differentiated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Ethanol increased Treg mitochondrial volume and altered expression of genes implicated in mitophagy and autophagosome formation (\n                    <jats:italic>PINK1<\/jats:italic>\n                    and\n                    <jats:italic>ATG7)<\/jats:italic>\n                    . These results suggest that ethanol impairs CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell immunometabolism and disrupts mitochondrial repair processes as it promotes CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation to a pro-inflammatory phenotype.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.839390","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T03:17:25Z","timestamp":1652325445000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["Alcohol Impairs Immunometabolism and Promotes Na\u00efve T Cell Differentiation to Pro-Inflammatory Th1 CD4+ T Cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Patrick M.","family":"McTernan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle 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