Transcriptional regulation of Th17 differentiation by mitochondrial oxidative phosphorylation. Transcriptional regulation of Th17 differentiation by mitochondrial oxidative phosphorylation

We found that mitochondrial oxidative phosphorylation (OXPHOS) plays a critical role in Th17 lineage specification. CD4 T cells differentiated under OXPHOS inhibited conditions show altered metabolic gene profiles (mitochondrial function, glycolysis, and TCA cycle) and pathways associated with cell proliferation. Furthermore, gene set enrichment analysis (GSEA) revealed that mitochondrial respiration impacts transcriptional profiles related to Th17 pathogenic signatures and BATF-sensitive gene clusters. Our study reveals a regulatory role of mitochondrial OXPHOS in transcriptional programming of Th17 lineage commitment. Overall design: Naïve CD4 T cells were differentiated into Th17 cells in the presence of vehicle (DMSO) or oligomycin (OXPHOS inhibitor) for 48 hours. Total mRNA profiles were generated by RNA sequencing in triplicate.