BALB/c mouse imiquimod-induced psoriasis model，IMQ psoriasis animal model，TLR7/8 innate immune inflammation，Th17-skewed psoriatic inflammation，anti-psoriatic drug screening model

The BALB/c mouse imiquimod cream-induced psoriasis model is a classic SCI gold-standard psoriasis animal model based on TLR7/8 innate immune activation and targeted IL-23/Th17 inflammatory axis, which is widely used for elucidating psoriasis pathogenesis, exploring epidermal hyperplasia mechanisms, and conducting preclinical pharmacodynamic evaluation of anti-psoriatic candidates. As a specific small-molecule agonist of TLR7/8, imiquimod (IMQ) activates cutaneous keratinocytes, dendritic cells and innate immune cells through continuous local skin stimulation, promotes the maturation and activation of dendritic cells, and induces the massive secretion of upstream pro-inflammatory factors such as IL-23 and IL-6. These cytokines further drive the polarization of CD4+ T cells into Th17 cells and trigger the cascading release of downstream core inflammatory mediators including IL-17A and IL-22. This immune cascade stably induces typical psoriasis vulgaris phenotypes in BALB/c mice, including erythema, silvery white scaling, skin thickening and abnormal keratinization. Pathologically, it recapitulates classic psoriatic lesions: parakeratosis, hyperkeratosis, acanthosis, elongated rete ridges, superficial dermal vasodilation and congestion, infiltration of neutrophils and lymphocytes, and characteristic Munro microabscesses. Compared with C57BL/6 mice, BALB/c mice exhibit more sensitive Th2/Th17 immune responses, milder and more uniform inflammatory phenotypes, and smaller individual differences. This model is highly suitable for the screening and mechanistic verification of drugs with anti-inflammatory, anti-scaling, anti-hyperplasia and Th17 immune regulatory effects, serving as a standardized mainstream model for basic psoriasis research and translational medicine.

SPF-grade BALB/c mice aged 6–8 weeks with a body weight of 18–22 g were used, and male mice were preferred. As a Th immune response-dominant strain, BALB/c mice are highly sensitive to IMQ-mediated TLR7/8 inflammatory activation, with uniform psoriatic lesions, minor inflammatory fluctuations and excellent reproducibility after modeling, which is the preferred experimental strain for psoriasis research compared with C57BL/6 mice. All mice were housed in an SPF barrier system with constant temperature and humidity, 12 h light/dark cycle, and ad libitum access to food and water. Formal modeling was initiated after 7 days of adaptive sterile feeding. Exogenous allergens, dust stimulation and breeding stress were strictly controlled throughout the experiment to ensure consistent immune status and synchronous lesion progression among all groups.

Modeling Success Criteria

Macroscopic Simplified PASI Score

The evaluation system includes three dimensions: erythema, scaling and skin thickening, with each item scored from 0 to 4 points and a total score ranging from 0 to 12 points. Score 0 indicates normal skin, and score 4 indicates the most severe symptoms. Mice in the model group presented typical psoriatic appearance including bright red erythema, multilayer silvery white scaling and skin hypertrophy. The total lesion score was significantly higher than that of the blank group with statistically significant differences, confirming successful modeling.

Quantitative Skin Thickness Index

The central thickness of dorsal lesions was uniformly measured by an electronic vernier caliper with fixed measurement sites and pressure. The skin thickness of the model group was significantly higher than that of the blank group, indicating obvious abnormal epidermal hyperplasia and dermal inflammatory edema, which was consistent with the pathological characteristics of psoriatic skin hypertrophy.

Histopathological Characteristics

HE staining results showed that the model group possessed all typical pathological phenotypes of psoriasis: epidermal hyperkeratosis and parakeratosis, characteristic Munro microabscesses in the stratum corneum, significant acanthosis and regularly elongated epidermal rete ridges. The superficial dermis presented vasodilation, congestion and tissue edema, with extensive infiltration of lymphocytes and neutrophils. The range and degree of inflammatory infiltration were significantly higher than those of the blank group.

Core Immunoinflammatory Indexes

The downstream factors of TLR7/8 and core inflammatory factors of the IL-23/Th17 axis (IL-17A, IL-22, IL-23, TNF-α, IL-6) in skin tissues and serum of the model group were significantly highly expressed, with persistent abnormal activation of the Th17 immune pathway, which served as the core gold-standard index for confirming the immunopathological success of the BALB/c mouse psoriasis model.

Model Advantages

As a standardized BALB/c mouse-specific psoriasis model, it presents more balanced and milder Th17 inflammatory responses and better lesion uniformity than the C57BL/6 strain, with minimal intra-group errors and excellent data reproducibility. Its modeling mechanism is highly consistent with the core TLR7/IL-23/Th17 pathogenesis axis of clinical psoriasis vulgaris. It has a short 7-day modeling cycle, extremely simple operation, no surgical trauma and 100% animal survival rate. It exhibits highly typical psoriatic characteristics including macroscopic scaling and erythema, pathological parakeratosis and microabscesses, with sensitive quantitative indexes and significant statistical differences. It is suitable for evaluating the anti-inflammatory, anti-proliferative and immunomodulatory efficacy of traditional Chinese medicines, natural products, topical creams and gels, and small-molecule targeted drugs, with highly recognized data for project application, graduation thesis and SCI publication.

Research Applications

The BALB/c mouse imiquimod cream-induced psoriasis model is specially used to clarify the mechanism of TLR7/8-mediated cutaneous innate immune activation, IL-23/Th17 inflammatory axis imbalance and abnormal keratinocyte proliferation in psoriasis. It serves as a core standard model for screening topical and oral candidate drugs with anti-inflammatory, anti-erythema, anti-scaling, anti-epidermal hyperplasia and Th17 immune regulatory effects. It is widely applied in preclinical pharmacodynamic evaluation and target mechanistic verification of traditional Chinese medicine compounds, natural active ingredients, small chemical molecules and topical skin preparations, acting as an essential gold-standard model for basic psoriasis immunology and skin inflammation translational research.