2. Academic Validation
  3. Celastrol gel ameliorates imiquimod-induced psoriasis-like dermatitis in mice by targeting Langerhans cells

Celastrol gel ameliorates imiquimod-induced psoriasis-like dermatitis in mice by targeting Langerhans cells

  • Biomed Pharmacother. 2022 Mar;147:112644. doi: 10.1016/j.biopha.2022.112644.
Liu Liu 1,  Xi Chen 2,  Yi Lu 3,  Xiao-Ying Sun 3,  Kan Ze 4,  Ya-Qiong Zhou 3,  Wei Li 5,  Xin Li 6,  Hong-Jin Li 7,  Bin Li 8
Affiliations

Affiliations

  • 1 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
  • 2 Department of Integrated TCM & Western Medicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China.
  • 3 Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China.
  • 4 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
  • 5 Institute of Dermatology, Shanghai Huashan Hospital, Shanghai 200040, China.
  • 6 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: 13661956326@163.com.
  • 7 Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: lhj215@163.com.
  • 8 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Department of Integrated TCM & Western Medicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: 18930568129@163.com.
PMID: 35051865 DOI: 10.1016/j.biopha.2022.112644
Abstract

Background: Psoriasis is an autoimmune disease mediated by T cells. However, treatment remains a clinical challenge because of its frequent recurrence. Celastrol (Cel), the main active ingredient in Tripterygium wilfordii Hook F, is efficacious in treating autoimmune diseases such as psoriasis.

Objective: To investigate the effect and mechanism of topical Cel in imiquimod (IMQ)-induced psoriasis-like inflammation in mice.

Methods: Female C57BL/6 and Langerin-diphtheria toxin receptor (DTR) mice were divided into Vehicle group and Cel gel groups. IMQ was used induce psoriasis-like inflammation to establish the mouse model of psoriasis. Hematoxylin and eosin staining was used to observe changes in local inflammatory cells in the skin lesions. Enzyme-linked immunosorbent assay was used to detect protein expression levels. Flow cytometry was used to detect the cell number and cytokine expression. Polymerase chain reaction was used to detect cytokine gene expression.

Results: Cel gel targeted the Langerhans cells. In IMQ-induced psoriatic dermatitis, Cel gel reduced the secretion of interleukin (IL)- 23 by Langerhans cells, suppressed the interaction between Langerhans cells and γδT cells, and decreased the number of activated γδT cells and related IL-17 secretion, alleviating psoriasis-like inflammation. Furthermore, Cel gel demonstrated a glucocorticoid-like effect that could impede the recurrence of psoriasis.

Conclusion: Cel gel reduces the secretion of IL-23 from LCs and inhibits the interaction between LCs and γδT cells to alleviate psoriasis. It also shows an effect similar to that of glucocorticoids, which can prevent psoriasis recurrence. These findings provide a new direction for the clinical treatment of psoriasis and contribute to the development of novel drugs.

Keywords

Celastrol; Langerhans cells; Psoriasis; γδT cells.

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