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Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation.
- Source :
-
Signal transduction and targeted therapy [Signal Transduct Target Ther] 2022 Jul 11; Vol. 7 (1), pp. 222. Date of Electronic Publication: 2022 Jul 11. - Publication Year :
- 2022
-
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 <superscript>+</superscript> CD4 <superscript>+</superscript> T cells, CD25 <superscript>+</superscript> CD4 <superscript>+</superscript> T cells, interferon (IFN)-γ-producing CD8 <superscript>+</superscript> T cells, Brdu <superscript>+</superscript> CD8 <superscript>+</superscript> 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.<br /> (© 2022. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2059-3635
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Signal transduction and targeted therapy
- Publication Type :
- Academic Journal
- Accession number :
- 35811310
- Full Text :
- https://doi.org/10.1038/s41392-022-01028-5