Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia.

ABSTRACT: The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown. Using a Pseudomonas aeruginosa-induced pneumonia model, we reported that IL-10-producing B cells (IL-10⁺ B cells) play a key role in spontaneously resolving infection-mediated inflammation. Accumulated cytosolic reactive oxygen species (ROS) during inflammation were shown to drive IL-10⁺ B-cell generation by remodeling one-carbon metabolism. Depletion of the enzyme serine hydroxymethyltransferase 1 (Shmt1) led to inadequate one-carbon metabolism and decreased IL-10⁺ B-cell production. Furthermore, increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine (SAM), altering histone H3 lysine 4 methylation (H3K4me)

SUBMITTER: Fu Y 

PROVIDER: S-EPMC10757717 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature