Oxidative phosphorylation regulates interleukin-10 production in regulatory B cells via the extracellular signal-related kinase pathway

Regulatory B cells (Bregs) are immune cells that constrain autoimmune 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 mitochondria' 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. Furthermore, suppression of OXPHOS diminished the expression of surface markers for Bregs and impaired their therapeutic effects in dextran sulphate sodium (DSS)-induced colitis. Mechanistically, mitochondrial OXPHOS was found to regulate the transcription factor HIF-1 alpha 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.

Automated summary

This study reveals the crucial role of mitochondrial oxidative phosphorylation (OXPHOS) in regulating interleukin (IL)-10 expression in regulatory B cells (Bregs). Inhibition of OXPHOS reduces IL-10 expression in B cells and impairs the therapeutic effects of Bregs in colitis. The study also demonstrates a strong correlation between mitochondrial OXPHOS and Breg phenotype/function and suggests OXPHOS as a potential therapeutic target for autoimmune diseases.