Performing efficacy studies using psoriasis models
Psoriasis arises due to the dysregulation of the interplay between the innate and adaptive immune system together with other compartments such as epithelium, vasculature, and cutaneous nervous system. On the cellular level, psoriasis is characterized by an increase in immune cells that produce a high number of cytokines, chemokines, and inflammatory molecules.
Modelling the human course of psoriasis in animal models often proves to be challenging because no rodent models can mimic all aspects of the disease. Nonetheless, multiple studies have shown that activating the relevant inflammatory pathways in mouse skin induces many of the hallmarks of psoriasis (1,2,3). Therefore, the acute skin inflammation psoriasis model represents a time- and money-efficient way to model psoriasis in vivo, especially if quick initial efficacy data need to be generated.
Acute skin inflammation (IL-23 induced) psoriasis model
IL-23 is a key cytokine produced by antigen-presenting cells that is necessary for the development of pathogenic lymphocytes that drive abnormal differentiation of keratinocytes and inflammation, the hallmarks of psoriasis.
When injected into mouse ear, recombinant IL-23 has been reported to increase ear thickness and inflammatory cell infiltration across multiple studies (2,3). Moreover, researchers have identified that many of the features in this model, such as IL-22 upregulation, epidermal hyperplasia, and pStat3 activation, are similar to features observed in psoriasis patients (3). In turn, multiple studies have concluded that the IL-23 injection psoriasis model is the closest to the human disease, although it does not model some disease features such as the influx of epidermal CD8+ T cells (2,3).
Therefore, it has been concluded that the recombinant IL-23 injection psoriasis model has the advantage of being a quick and effective way to acutely induce psoriasis in vivo.
Case study
The case study below outlines a study design to evaluate the efficacy of novel anti-psoriatic treatments in the acute skin inflammation psoriasis model. Download the case study below to discover:
- Typical study design with standard and optional readouts in the IL-23 induced psoriasis model (I.e., flow cytometry panels, gene expression level evaluation).
- Ear thickness and digital histopathology results showing the efficacy of a putative psoriasis treatment in the IL-23 induced psoriasis model.