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Oxidative Phosphorylation Regulates Interleukin-10 Production in Regulatory B Cells via the Extracellular Signal-related Kinase Pathway

ABSTRACT: Regulatory B cells (Bregs) are immune cells that constrain the immune response and restrict inflammation via their expression of interleukin (IL)-10. However, the molecular mechanisms underlying Breg differentiation and IL-10 secretion remain unclear. Previous data suggest that cellular metabolism determines both the fate and function of these cells. Here, we suggest an essential role for mitochondrial oxidative phosphorylation (OXPHOS) in the regulation of IL-10 in these Bregs. We found that IL-10+ B cells from IL-10-green fluorescent protein-expressing mice had higher oxygen consumption rate than IL-10- B cells. In addition, inhibition of OXPHOS decreased the expression of IL-10 in B cells. Further, suppression of OXPHOS diminished the expression of surface markers for Bregs and impaired their therapeutic effects in dextran sulfate sodium-induced colitis. Mechanistically, mitochondrial OXPHOS was found to regulate the transcription factor HIF-1α through the extracellular signal-related kinase pathway. Taken together, this study reveals a strong correlation between mitochondrial OXPHOS and Breg phenotype/function, indicating OXPHOS as a therapeutic target in autoimmune diseases driven by Breg dysfunction.

ORGANISM(S): Mus musculus

PROVIDER: GSE181765 | GEO | 2022/07/31

REPOSITORIES: GEO

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