Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation.
Signal Transduct Target Ther
; 7(1): 222, 2022 07 11.
Article
in En
| MEDLINE
| ID: mdl-35811310
ABSTRACT
Artemisinin (ART) and dihydroartemisinin (DHA), apart from their profound anti-malaria effect, can also beneficially modulate the host immune system; however, the underlying molecular mechanisms remain unclear. Here, we report that DHA selectively induced T-cell activation, with an increased proportion of Ki67+CD4+ T cells, CD25+CD4+ T cells, interferon (IFN)-γ-producing CD8+ T cells, Brdu+ CD8+ T cells and neutrophils, which was found to enhance cellular immunity to experimental malaria and overcome immunosuppression in mice. We further revealed that DHA upregulated the expression of cell proliferation-associated proteins by promoting the phosphorylation of mitogen-activated protein kinase (MAPK), cyclin-dependent kinases (CDKs), and activator protein 1 in the spleen. This study is the first to provide robust evidence that DHA selectively induced the expansion of subsets of splenic T cells through phosphorylated CDKs and MAPK to enhance cellular immune responses under non-pathological or pathological conditions. The data significantly deepened our knowledge in the mechanism underlying DHA-mediated immunomodulation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitogen-Activated Protein Kinases
/
Artemisinins
Limits:
Animals
Language:
En
Journal:
Signal Transduct Target Ther
Year:
2022
Document type:
Article
Affiliation country:
China