In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-12)
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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.839390
DOI:
10.3389/fimmu.2022.839390.s001
DOI:
10.3389/fimmu.2022.839390.s002
DOI:
10.3389/fimmu.2022.839390.s003
DOI:
10.3389/fimmu.2022.839390.s004
DOI:
10.3389/fimmu.2022.839390.s005
DOI:
10.3389/fimmu.2022.839390.s006
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8