Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis

作     者：Yiwei Zhang Qilong Li Ning Jiang Ziwei Su Quan Yuan Lei Lv Xiaoyu Sang Ran Chen Ying Feng Qijun Chen 

作者机构：Key Laboratory of Livestock Infectious Diseases in Northeast ChinaMinistry of EducationKey Laboratory of ZoonosisCollege of Animal Science and Veterinary MedicineShenyang Agricultural UniversityShenyang 110866China Research Unit for Pathogenic Mechanisms of Zoonotic ParasitesChinese Academy of Medical SciencesShenyang 110866China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2022年第65卷第8期

页      面：1636-1654页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (82030060) CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-042) 

主　　题：dihydroartemisinin immunomodulatory activity single-cell RNA sequencing AP-1 transcription factor SOD3 

摘      要：The immunomodulatory potential of dihydroartemisinin(DHA) has recently been highlighted;however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular and biochemical approaches to elucidate the immunomodulatory mechanisms of DHA. In this study, we found that DHA induced both spleen enlargement and rearrangement of splenic immune cell subsets in mice. It was revealed that DHA promoted the reversible expansion of effective regulatory T cells and interferon-γ^(+)cytotoxic CD8^(+)T cells in the spleen via induction of superoxide dismutase 3(SOD3) expression and increased phosphorylation of c-Jun N-terminal kinases(JNK) and its downstream activator protein 1(AP-1) transcription factors. Further, SOD3 knockout mice were resistant to the regulatory effect of DHA. Thus, DHA,through the activation of the SOD3-JNK-AP-1 axis, beneficially regulated immune cell heterogeneity and splenic immune cell homeostasis to treat autoimmune diseases.