Abstract: 【Abstract】 Objective To determine S100A10 protein expression in psoriatic lesions, and to investigate its effect on psoriasis-like skin inflammation in imiquimod （IMQ）-induced mouse models. Methods From January 2020 to June 2022, skin lesions were surgically collected from 28 patients with psoriasis in the Department of Dermatology, the First Affiliated Hospital of Xinxiang Medical University; normal skin tissues were collected from 18 healthy subjects in the Department of General Surgery and Department of Ophthalmology during the same period, and served as a control group. Immunohistochemical staining was performed to determine the S100A10 protein expression in skin lesions from psoriasis patients and normal skin tissues from healthy controls. Ten wild-type （WT） C57BL/6J female mice and 10 S100A10-/- C57BL/6J female mice were selected to establish the IMQ-induced mouse models of psoriasis-like skin inflammation. Then, the mice were randomly divided into gene knock-out （KO）/IMQ group, WT/IMQ group, KO/vaseline （VAS） group, and WT/VAS group by using a random number table, and there were 5 mice in each group. The mice in the KO/IMQ group and WT/IMQ group were topically treated with IMQ cream （62.5 mg） on the shaved back daily to establish the mouse models of psoriasis-like skin inflammation, while the mice in the KO/VAS group and WT/VAS group were topically treated with vaseline cream （62.5 mg） daily, and both treatments lasted 7 consecutive days. Skin lesions on the back were observed daily. On day 7, the mice were sacrificed by cervical dislocation, and their dorsal skin tissues were excised. The IMQ-induced psoriasis-like skin inflammation was evaluated by the psoriasis area and severity index （PASI）, pathological manifestations of skin lesions were observed by hematoxylin and eosin staining, the expression of S100A10 and Ki-67 in skin lesions was determined by immunohistochemical staining, the expression of STAT3, IL-17A and other cytokines was determined by Western blot analysis, and IL-17 mRNA expression was determined by real-time fluorescence-based quantitative PCR （qPCR）. Statistical analysis was carried out by using the independent sample t-test, nonparametric U test, and chi-square test. Results Immunohistochemical staining showed that the S100A10 protein expression was significantly lower in the psoriasis vulgaris lesions than in the normal control skin tissues （Z = -3.47, P < 0.001）. In the mouse models, the S100A10 protein expression was significantly lower in the skin lesions of mice in the WT/IMQ group than in the skin tissues of mice in the WT/VAS group （t = 3.64, P = 0.007）, and the Ki-67 expression was significantly higher in the KO/IMQ group than in the WT/IMQ group （t = 2.97, P = 0.041）. Additionally, the mice in the KO/IMQ group presented with more severe clinical manifestations such as scales and infiltration compared with those in the WT/IMQ group. Western blot analysis showed that the phosphorylated STAT3/STAT3 expression and IL-17A protein expression was significantly higher in the KO/IMQ group than in the WT/IMQ group （t = 3.27, 3.48, P = 0.031, 0.025, respectively）, and qPCR revealed that the IL-17A mRNA expression was also significantly higher in the KO/IMQ group than in the WT/IMQ group （t = 2.73, P = 0.029）. Conclusion S100A10 protein was underexpressed in the skin lesions of psoriasis patients, and the deletion of S100A10 protein aggravated IMQ-induced psoriasis-like skin inflammation in mice, possibly by upregulating STAT3 phosphorylation in the epidermis.

Key words: Psoriasis, Disease models, animal, STAT3 transcription factor, Interleukin-17, Ki-67 antigen, S100A10, Interleukin-17A