2. Academic Validation
  3. Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation

Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation

  • Signal Transduct Target Ther. 2022 Jul 11;7(1):222. doi: 10.1038/s41392-022-01028-5.
Qilong Li  # 1 2,  Quan Yuan  # 1 2,  Ning Jiang  # 1 2,  Yiwei Zhang 1 2,  Ziwei Su 1 2,  Lei Lv 1 2,  Xiaoyu Sang 1 2,  Ran Chen 1 2,  Ying Feng 1 2,  Qijun Chen 3 4
Affiliations

Affiliations

  • 1 Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, 110866, Shenyang, China.
  • 2 Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, 110866, Shenyang, China.
  • 3 Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, 110866, Shenyang, China. qijunchen759@syau.edu.cn.
  • 4 Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, 110866, Shenyang, China. qijunchen759@syau.edu.cn.
  • # Contributed equally.
PMID: 35811310 DOI: 10.1038/s41392-022-01028-5
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.

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