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

作     者：Ying Fu Baichao Yu Qi Wang Zhou Lu Hushan Zhang Dan Zhang Feifei Luo Ronghua Liu Luman Wang Yiwei Chu 

作者机构：Department of ImmunologySchool of Basic Medical SciencesShanghai Key Laboratory of Medical Epigenetics and MetabolismInstitutes of Biomedical SciencesFudan UniversityShanghaiChina Zhongshan Hospital Institute of Clinical ScienceZhongshan HospitalShanghaiChina Zhaotong Health Vocational CollegeZhaotongYunnanChina Department of Digestive DiseasesHuashan HospitalFudan UniversityShanghaiChina Shanghai Fifth People’s HospitalFudan UniversityShanghaiChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2024年第21卷第1期

页      面：19-32页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：supported by the General Program of the National Natural Science Foundation of China(81971493,81771736) the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(82121002) Major Program of National Natural Science Foundation of China(821300501,82330053) Shanghai Rising-Star Program(20QA1407900) Innovative Research Team of High-level Local Universities in Shanghai. 

主　　题：IL-10-producing B cell Reactive oxygen species One-carbon metabolism H3K4me Pneumonia 

摘      要：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)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.