Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China.
Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, 110866, China.
Sci China Life Sci. 2022 Aug;65(8):1636-1654. doi: 10.1007/s11427-021-2061-7. Epub 2022 Feb 23.
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.
二氢青蒿素（DHA）的免疫调节潜力最近受到了关注；然而，其潜在的机制仍有待阐明。本研究采用单细胞 RNA 测序结合细胞和生化方法，阐明了 DHA 的免疫调节机制。研究发现，DHA 可诱导小鼠脾脏肿大和脾脏免疫细胞亚群重排。研究结果表明，DHA 通过诱导超氧化物歧化酶 3（SOD3）表达和增加 c-Jun N 端激酶（JNK）及其下游激活蛋白 1（AP-1）转录因子的磷酸化，促进有效调节性 T 细胞和干扰素-γ细胞毒性 CD8 T 细胞在脾脏中的可逆扩增。此外，SOD3 敲除小鼠对 DHA 的调节作用具有抗性。因此，DHA 通过激活 SOD3-JNK-AP-1 轴，有益地调节免疫细胞异质性和脾脏免疫细胞动态平衡，从而治疗自身免疫性疾病。
