부산대학교 도서관

Metabolic programming is important for B cell fate, but the bioenergetic requirement for regulatory B (Breg) cell differentiation and function is unknown. Here we show that Bregcell differentiation, unlike non-Bregcells, relies on mitochondrial electron transport and homeostatic levels of reactive oxygen species (ROS). Single-cell RNA sequencing analysis revealed that TXN, encoding the metabolic redox protein thioredoxin (Trx), is highly expressed by Bregcells, unlike Trx inhibitor TXNIPwhich was downregulated. Pharmacological inhibition or gene silencing of TXNresulted in mitochondrial membrane depolarization and increased ROS levels, selectively suppressing Bregcell differentiation and function while favoring pro-inflammatory B cell differentiation. Patients with systemic lupus erythematosus (SLE), characterized by Bregcell deficiencies, present with B cell mitochondrial membrane depolarization, elevated ROS and fewer Trx+B cells. Exogenous Trx stimulation restored Bregcells and mitochondrial membrane polarization in SLE B cells to healthy B cell levels, indicating Trx insufficiency underlies Bregcell impairment in patients with SLE.