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.

本研究发现线粒体氧化磷酸化（mitochondrial oxidative phosphorylation, OXPHOS）在Th17细胞谱系特化过程中发挥关键调控作用。在OXPHOS抑制条件下分化的CD4 T细胞，其代谢基因表达谱（涵盖线粒体功能、糖酵解与三羧酸循环）及细胞增殖相关通路均发生显著改变。此外，基因集富集分析（gene set enrichment analysis, GSEA）结果显示，线粒体呼吸作用可影响与Th17细胞致病特征及BATF敏感基因簇相关的转录谱。本研究阐明了线粒体OXPHOS在Th17细胞谱系定型的转录编程中的调控功能。整体实验设计：初始CD4 T细胞在溶剂对照（二甲基亚砜，DMSO）或寡霉素（OXPHOS抑制剂）存在的条件下分化为Th17细胞，培养48小时。采用RNA测序技术对三组生物学重复样本的总mRNA表达谱进行检测。