Dihydroartemisinin (DHA) is a derivative of artemisinin
Not only is it the drug of choice for the treatment of malaria, it is also used to treat autoimmune diseases such as systemic lupus erythematosus and psoriasis
After DHA was first reported to have immunomodulatory effects in the 1990s, more and more evidences have shown that DHA can modulate the body's immune system, but its underlying regulatory mechanism remains to be revealed
Recently, Professor Chen Qijun's research group from Shenyang Agricultural University published a research paper entitled "Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis" in Science China Life Sciences, revealing that DHA regulates SOD3-JNK- AP-1 signaling pathway regulates the body's immune system
In a previous study, Prof.
Qijun Chen's group found that DHA can cause the rearrangement of immune cells in the spleen of mice (Zhang et al.
, Science China Life Sciences, 2020)
On this basis, the research group used single-cell transcriptome sequencing technology to construct the first cellular transcriptional map of DHA-regulated spleen immune cell subsets
In terms of cellular immunity, the research group found and verified that the proportion of spleen regulatory T cells (Treg) and CD8+IFN-γ+cytotoxic T cells was significantly increased after DHA intervention
At the same time, Treg highly expressed inhibitory signal molecules such as CD73, CD274 and IL-10, while the expression of key effector molecules granzyme A and granzyme B in CD8+IFN-γ+ cytotoxic T cells was down-regulated
In terms of humoral immunity, the research group found that after DHA intervention, the expression of MHCII molecules in spleen follicular B cells was down-regulated; at the same time, the expression levels of key molecules (CD79a, CD79b and Ms4a1) related to B cell activation in follicular B cells were also decreased.
These results suggest that DHA has distinct effects on humoral and cellular immunity
Analysis of KEGG enrichment and differential gene expression showed that DHA significantly up-regulated the expression of Activating Protein-1 (AP-1) transcription factor in various immune cells
The research group used flow cytometry and Western Blot and other experimental techniques to confirm that the changes in the expression of AP-1 and its upstream kinase JNK are indeed regulated by DHA
Studies have shown that superoxide dismutase 3 (SOD3), as a growth regulator, can drive the activation of AP-1
The research group used SOD3 knockout mice to study, and confirmed that SOD3 knockout can inhibit DHA-induced immune cell rearrangement and activation of JNK-AP-1 signaling pathway
This indicates that the immunoregulatory function of DHA is indeed closely related to the activation of SOD3-JNK-AP-1 signaling pathway
This study lays a foundation for in-depth understanding and revealing of the immune regulation function and molecular mechanism of DHA
DHA-mediated immune regulation in the spleen and its underlying mechanisms.
Lecturer Zhang Yiwei, Dr.
Li Qilong and Professor Jiang Ning from the School of Animal Science and Medicine, Shenyang Agricultural University are the co-first authors of the article, and Professor Chen Qijun is the corresponding author
For details, please read the original text▼[Click the link below or read the original text]Zhang, Y.
, Li, Q.
, Jiang, N.
, Su, Z.
, Yuan, Q.
, Lv, L.
, Sang, X.
, Chen , R.
, Feng, Y.
, and Chen, Q.
Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis.
Sci China Life Sci 65, https://doi.