Journal
SIGNAL TRANSDUCTION AND TARGETED THERAPY
Volume 7, Issue 1, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41392-022-01028-5
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Funding
- National Nature and Science Foundation of China [82030060]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2019-I2M-5-042]
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DHA selectively induces expansion of subsets of splenic T cells through phosphorylated CDKs and MAPK, enhancing cellular immune responses.
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)-gamma-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.
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