Thioredoxin is a metabolic rheostat controlling regulatory B cells
Hannah F. Bradford, Thomas C. R. McDonnell, Alexander Stewart, Andrew Skelton, Joseph Ng, Zara Baig, Franca Fraternali, Deborah Dunn-Walters, David A. Isenberg, Adnan R. Khan, Claudio Mauro, Claudia Mauri
TL;DR
Thioredoxin helps control regulatory B cells by managing mitochondrial energy and reactive oxygen species, which is important in diseases like lupus.
Contribution
The study identifies thioredoxin as a key metabolic regulator of regulatory B cell function and its role in systemic lupus erythematosus.
Findings
Breg cell differentiation depends on mitochondrial electron transport and ROS homeostasis.
Thioredoxin is highly expressed in Breg cells and its inhibition suppresses their function.
Exogenous Trx restores Breg cell function in SLE patients by normalizing mitochondrial and ROS levels.
Abstract
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 Breg cell differentiation, unlike non-Breg cells, 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 Breg cells, unlike Trx inhibitor TXNIP which was downregulated. Pharmacological inhibition or gene silencing of TXN resulted in mitochondrial membrane depolarization and increased ROS levels, selectively suppressing Breg cell differentiation and function while favoring pro-inflammatory B cell differentiation. Patients with systemic lupus erythematosus (SLE), characterized by Breg cell deficiencies, present with B cell mitochondrial…
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Taxonomy
TopicsEnvironmental and Ecological Studies · Wind and Air Flow Studies