Inflammation and Autoimmunity

Psoriasis

Biocytogen provides an imiquimod-induced psoriasis model to support drug discovery efforts. Notably, we have developed a series of target humanized mice, such as the B-hIL17A mice, in which the human IL-17A gene replaces the mouse IL-17A gene. This genetically humanized psoriasis model provides a robust platform for convenient and effective therapeutic testing.

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  • Psoriasis Model Introduction
  • Results

Publication

    Psoriasis Model Introduction

    Psoriasis is a type of skin disease characterized by hyperproliferation of the epidermal keratinocytes. It is thought to be mediated by cells and molecules of both the innate and adaptive immune systems, as a result of a combination of genetic, epigenetic, and environmental influences. The most commonly used animal model is the imiquimod (IMQ)-induced skin lesion and skin inflammation, which phenotypically resembles human psoriasis.

    The degree of imiquimod-induced skin injury in this murine psoriasis model, with symptoms of skin rashes and peeling in mice, can be monitored through a standard clinical score system. The cutaneous epidermis is thickened. Parakeratosis and inflammatory infiltration of leukocytes predominantly into dermis can be seen histopathologically. The IL-23/IL-17 axis is believed to be particularly important in psoriasis pathogenesis due to its pro-inflammatory effects. IL-17 cytokine level is elevated in the imiquimod-induced psoriasis model.

    Biocytogen provides a humanized imiquimod-induced psoriasis model for your psoriasis drug discovery applications. In particular, we generated B-hIL17A mice where the human IL-17A gene is knocked-in and replaces the mouse IL-17A gene. This genetically humanized mouse psoriasis model allows for for convenient testing of therapeutics targeting human IL-17A.

    Results
    Establishment of Psoriasis Mouse Model
    • Experimental Animals: C57BL/6 or Balb/c, B-hIL17A/hIL17F mice, 7-8 weeks old, female
    • Modeling reagent: Imiquimod (IMQ) cream
    • Modeling method: Topically applicated on dorsal for consecutive 5-8 days, depends on the mouse strain.
    Readouts
    Clinical scores Erythema
    Scaling
    Histopathology Dorsal skin epidermal thickness
    Histology scores
    (epidermal hyperplasia, parakeratosis and hyperkeratosis, erosion, inflammatory infiltration)
    Molecular levels Skin IL17, IL23 levels
    In Vivo Efficacy of Dexamethasone in a Psoriasis Model of C57BL/6 Mice

    Dexamethasone (Dex) improved clinical scores in IMQ-induced psoriasis of C57BL/6 mice. A. Body weight change during treatment. B. Daily erythema scores. C. Daily scaling scores. D. cumulative score of each group. E. Area under the cumulative score curve in each group. (B-C. Two-way ANOVA; E. One-way ANOVA; ** p< 0.01, **** p< 0.0001).

    Dexamethasone inhibited keratinocyte proliferation and inflammatory cell infiltration in psoriasis model of C57BL/6 mice. A. H&E staining of dorsal skin. B. Mouse epidermal thickness. C. Histopathology score. (One-way ANOVA; **** p< 0.0001).

    In Vivo Efficacy of Dexamethasone in a Psoriasis Model of BALB/c Mice

    Dexamethasone (Dex) improved clinical scores in IMQ-induced psoriasis of BALB/c mice. A. erythema scores on day 8. B. scaling scores on day 8. C. cumulative score on day 8. D. Daily erythema scores. E. Daily scaling scores. F. cumulative score of each group. (B-C. Two-way ANOVA; E. One-way ANOVA; ** p< 0.01, **** p< 0.0001).

    In Vivo Efficacy of Bimekizumab (in-house) in a Psoriasis Mouse Model of B-hIL17A/hIL17F Mice

    Bimekizumab improved IMQ-induced psoriasis in B-hIL17A/hIL17F mice. A. Daily erythema scores. B. Daily scaling scores. C. cumulative score of each group. D. Area under the cumulative score curve in each group. E. H&E staining of dorsal skin. F. epidermal thickness. G. Histopathology score. (Two-way ANOVA or One-way ANOVA; * p< 0.05 , *** p< 0.001, **** p< 0.0001).