Dihydroartemisinin imposes positive and negative regulation on Treg and plasma cells via direct interaction and activation of c-Fos

  • Commun Biol. 2023 Jan 16;6(1):52. doi: 10.1038/s42003-023-04454-5.
Qilong Li  #  1  2 ,  Ning Jiang  #  1  2 ,  Yiwei Zhang  1  2 ,  Yize Liu  1  2 ,  Ziwei Su  1  2 ,  Quan Yuan  1  2 ,  Xiaoyu Sang  1  2 ,  Ran Chen  1  2 ,  Ying Feng  1  2 ,  Qijun Chen  3  4
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, Shenyang, 110866, China.
  • 2. Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866, 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, Shenyang, 110866, China. [email protected].
  • 4. Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, 120 Dongling Road, Shenyang, 110866, China. [email protected].
  • # Contributed equally.
PMID: 36646927 DOI: 10.1038/s42003-023-04454-5
Abstract

Dihydroartemisinin (DHA), a potent antimalarial drug, also exhibits distinct property in modulation on Treg and B cells, which has been recognized for decades, but the underlying mechanisms remain understood. Herein we revealed that DHA could promote Treg proliferation, meanwhile, suppress B cell expansion in germinal centers, and consequently decrease the number of circulating plasma cells and the content of serum immunoglobulins. Further, DHA-activated Treg significantly mitigated lipopolysaccharide-induced and malaria-associated inflammation. All these scenarios were attributed to the upregulation of c-Fos expression by DHA and enhancement of its interaction with target genes in both Treg and circulating plasma cells with bilateral cell fates. In Treg, the c-Fos-DHA complex upregulated cell proliferation-associated genes and promoted cell expansion; whereas in plasma cells, it upregulated the apoptosis-related genes resulting in decreased circulating plasma cells. Thus, the bilateral immunoregulatory mechanism of DHA was elucidated and its application in the treatment of autoimmune diseases is further justified.

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