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  3. The opposite effect of tapinarof between IMQ and IL-23 induced psoriasis mouse models

The opposite effect of tapinarof between IMQ and IL-23 induced psoriasis mouse models

  • Exp Dermatol. 2023 Jun 23. doi: 10.1111/exd.14862.
Xingyu Zhu 1 2,  Ruomei Han 1,  Xiaoxue Tian 3,  Mathias Hochgerner 3,  Hui Li 4,  Jiucun Wang 1 3 5,  Jingjing Xia 1 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
  • 2 Institute for Six-Sector Economy, Fudan University, Shanghai, China.
  • 3 Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, Shanghai, China.
  • 4 MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
  • 5 Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, China.
PMID: 37350230 DOI: 10.1111/exd.14862
Abstract

Tapinarof is an Aryl Hydrocarbon Receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL-23. Although both models successfully induced psoriasis-like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL-23/IL-17/IL-22 axis and ameliorated IMQ-induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL-23-injection-model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis.

Keywords

imiquimod; interleukin-23; psoriasis; tapinarof.

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