AUTHOR=Liu Jiang-Min , Jin Quan-Xin , Fujimoto Manabu , Li Fang-Fang , Jin Lin-Bo , Yu Ran , Yan Guang-Hai , Zhu Lian-Hua , Meng Fan-Ping , Zhang Qing-Gao , Jin Gui-Hua 

TITLE=Dihydroartemisinin Alleviates Imiquimod-Induced Psoriasis-like Skin Lesion in Mice Involving Modulation of IL-23/Th17 Axis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.704481

DOI=10.3389/fphar.2021.704481

ISSN=1663-9812

ABSTRACT=Background: Psoriasis is a Th17 cells-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.
Objective: To verify whether DHA can improve the symptoms of psoriasis, and to further explore the possible mechanism.
Methods: The efficiency of DHA was preliminary detected on HaCaT cells in psoriatic condition. Then imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo. 
Results: Under the stimulation of TNF-α and IFN-γ, DHA inhibited the proliferation of HaCaT cells, and significantly affected the mRNA expression levels of IFN-γ, IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is make up of the T cells, dendritic cells and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and expression of Th17 cell-related transcription factors ROR-γt in vitro. In addition, phosphorylation of STAT3 was significantly reduced in DHA treatment mice, suggesting that the IL-23/IL-17 axis plays a pivotal role. 
Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis, and is expected to be an effective drug for the treatment of psoriasis.