Mechanistic and pharmacological assessment of murine IL-23 mediated psoriasiform dermatitis; implications for drug discovery

Publication date: Available online 7 August 2018

Source: Journal of Dermatological Science

Author(s): Stephen B. Gauld, Donna Gauvin, Lauren Olson, Laura Leys, Stephanie Paulsboe, Zheng Liu, Rebecca M. Edelmayer, Joseph Wetter, Katherine Salte, Yibing Wang, Susan Huang, Prisca Honore, Steven McGaraughty

Abstract

Background

Animal models of Psoriasis (PsO) are important for our understanding of the pathophysiology of human disease but rarely manifest all features of the disease. In order to facilitate greater understanding of the underlying biology of PsO it is key that we understand the strengths and limitations of models used.

Objective

While humanized mouse models are available for PsO they remain technically challenging, expensive, require prolonged timelines and require a continued source of human tissue. Another approach is to focus on developing mechanistic models which recapitulate key features of human PsO. The role of the IL-23/IL-17 pathway as a key driver of human PsO is both well characterized and clinically validated. The goal of this manuscript is to provide a comprehensive disease and pharmacological assessment of IL-23 driven skin inflammation and its similarity to human psoriatic skin.

Methods

Intradermal injection of IL-23 has been used to study the IL-23 pathway in rodents, and this current study further characterizes pathology, cellular infiltrate, and gene signature kinetics, as well as the modulation of disease features by clinically relevant agents.

Results

Our results indicate that IL-23 triggers an early and robust activation of the immune system resulting in accumulation of T cell and monocyte/macrophage populations. It also supports changes in gene expression that parallel those observed in human psoriasis samples and is responsive to biologics commonly used to treat PsO in the clinic.

Conclusions

Collectively, our studies indicate that a 5 day model of IL-23 psoriasiform dermatitis can be used to assess the pharmacology of novel small molecules/biologics in the treatment of PsO.

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