Background Psoriasis is a chronic autoimmune skin disease characterized by aberrant keratinocyte proliferation and inflammatory cell infiltration.^{1 2} Nonhuman primates (NHP) have contributed greatly to pre-clinical drug evaluation during the last decades due to the high-level genetic homology.³ However, the lack of a suitable NHP model mimicking the complex phenotype of this skin disorder limits the development of promising psoriasis therapeutics. Here, a specific focus has been given on imiquimod to generate biological and pathological symptoms of psoriasis in rhesus monkeys and further promote the efficacy evaluation study of potential psoriasis drugs.

Methods 9 rhesus monkeys were selected and divided into the model group (n=4) and the treatment group (n=5). The monkeys from the treatment group were pre-treated with deucravacitinib orally once daily, and then all monkeys were treated with imiquimod topically twice daily on the dorsal back to induce psoriasis-like symptoms. During the study, the general health, trans epidermal water loss (TEWL), and the clinical score of imiquimod-treated areas were monitored. Moreover, tissue samples of imiquimod-treated skin were isolated for assessments for cytokine and histopathology.

Results After rubbing of imiquimod in rhesus monkeys, the typical features of induration, redness, and crusting were distinctly observed, accompanied by a significant increase of TEWL and clinical score. Histopathology analysis of the skin biopsy indicated obvious hyperkeratosis and inflammatory cell infiltration, together with an upregulation of Th1 and Th17 cell-dependent and psoriasis-associated signaling pathways and elevated mRNA levels of psoriasis-associated cytokines, suggesting that imiquimod could induce psoriasis-like skin inflammation. While, deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor approved for the treatment of psoriasis, remarkably relieved these symptoms, downregulated relevant biomarkers, and thus indicated a strong remission effect.

Conclusions In this study, we established a psoriasis NHP model by topically applying imiquimod on the dorsal skin of rhesus monkeys, which imitated the similar pathological symptoms of human psoriasis involving clinical appearance, pathological features, and inflammatory cytokine changes. Our study reveals that the psoriasis model in rhesus monkeys could be considered as a novel biological tool for pre-clinical PK/PD study and screening of anti-psoriasis related therapeutics.

References

1. Armstrong April W, Charlotte Read. ‘Pathophysiology, clinical presentation, and treatment of psoriasis: a review.’ JAMA 2020;323(19):1945–1960.

2. Boehncke Wolf-Henning, Michael P Schön. ‘Psoriasis.’ Lancet (London, England) 2015;386(9997):983–94.

3. Harding John D. ‘Nonhuman primates and translational research: progress, opportunities, and challenges.’ ILAR Journal 2017;58(2):141–150.

Ethics Approval This study was approved by WuXi AppTec Institutional Animal Care and Use Committee (IACUC) institution’s Ethics Board; approval number AM13-CD024-2023v1.1.