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

Cell Mol Immunol. 2023 Dec 11. doi: 10.1038/s41423-023-01109-7. Online ahead of print.ABSTRACTThe 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) at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells. Therefore, the one-carbon metabolism-associated compound ethacrynic acid (EA) was screened and found to potentially treat infectious pneumonia by boosting IL-10+ B-cell generation. Overall, these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.PMID:38082147 | DOI:10.1038/s41423-023-01109-7
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Source Type: research