Journal
SCIENCE CHINA-LIFE SCIENCES
Volume 65, Issue 8, Pages 1636-1654Publisher
SCIENCE PRESS
DOI: 10.1007/s11427-021-2061-7
Keywords
dihydroartemisinin; immunomodulatory activity; single-cell RNA sequencing; AP-1 transcription factor; SOD3
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Funding
- National Natural Science Foundation of China [82030060]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2019-I2M-5-042]
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This study reveals that dihydroartemisinin (DHA) regulates immune cell subsets and homeostasis in the spleen through the induction of superoxide dismutase 3 (SOD3) expression and activation of the JNK-AP-1 pathway, offering potential treatment for autoimmune diseases.
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-gamma(+) 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.
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