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

Dihydroartemisinin (DHA), a potent antimalarial drug, also exhibits distinct property in modulation on T-reg and B cells, which has been recognized for decades, but the underlying mechanisms remain understood. Herein we revealed that DHA could promote T-reg 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 T-reg 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 T-reg and circulating plasma cells with bilateral cell fates. In T-reg, 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.

Automated summary

Dihydroartemisinin (DHA) possesses immunomodulatory properties by promoting T-reg proliferation and suppressing B cell expansion. This is achieved through the upregulation of c-Fos expression, which enhances its interaction with target genes in both T-reg and circulating plasma cells, leading to different cell fates. DHA's immunoregulatory mechanism has been elucidated and its potential for the treatment of autoimmune diseases is further justified.