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Oxidative Stress-initiated One-carbon Metabolism drives Interleukin-10-producing B Cells to Resolute Pneumonia (ATAC-Seq)

ABSTRACT: Metabolic reprogramming for regulatory B cell generation in infectious diseases remains unknown. With a Pseudomonas aeruginosa-induced pneumonia model, we report IL-10-producing B cells (IL-10+B cells) are indispensable for spontaneous remission of the infection. The accumulation of cytosolic reactive oxygen species (ROS) is responsible for the IL-10 producing within B cells. Of note, ROS scavenging downregulated the one-carbon metabolism and the depletion of one-carbon metabolic methyl transfer enzyme serine hydroxymethyl transferase 1 (Shmt1) led to decreased IL-10+ B cells production both in vitro and in vivo. Mechanistically, one-carbon flux enhanced the availability of methyl groups, which altered histone H3 lysine 4 methylation at Il10 loci and led to massive IL-10 production in B cells. Therefore, the metabolic-associated drug ethacrynic acid (EA) was screened out and potentially restored infectious pneumonia accompanied by increased IL-10+ B cells. The results provide a new insight that ROS serve as modulators to resolute inflammation by reprogramming one-carbon metabolism in lung B cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE211326 | GEO | 2024/01/03

REPOSITORIES: GEO

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Oxidative Stress-initiated One-carbon Metabolism drives Interleukin-10-producing B Cells to Resolute Pneumonia (ATAC-Seq)

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