关键词: 银屑病； 小鼠, 近交C57BL； 受体, 抗原, T细胞, γ-δ； 白细胞介素17； 鞘氨醇1-磷酸盐受体

Abstract: 【Abstract】    Objective    To evaluate therapeutic effect of the sphingosine-1-phosphate receptor antagonist FTY720 on the imiquimod-induced psoriasis-like mouse model, and to explore its molecular mechanism. Methods    A total of 8 specific pathogen-free （SPF） female C57BL/6 mice were used in this study, and divided into experimental group（n = 3） and control group（n = 5）: each mouse ear was topically treated with 10 mg/d imiquimod for 7 consecutive days, and the experimental group and control group were intraperitoneally injected with FTY720 and phosphate buffer saline (PBS) respectively on days 2, 4 and 6. Ear skin thickness was measured every day. These mice were sacrificed on day 8, and histopathological changes of the ear skin were observed. The ear tissues and draining cervical lymph node cells were obtained. Flow cytometry was performed to analyze changes in the proportion of interleukin （IL）-17+ γδT cells in the mouse skin and draining lymph node tissues between the two above groups, and to determine the expression of sphingosine-1-phosphate receptor 1 （S1P1） and cutaneous lymphocyte antigen （CLA） on the surface of the γδT cells. The means of two independent samples were compared by using t test. Results    After the 2-day topical application of imiquimod, the mouse ear thickness was significantly lower in the experimental group （0.217 mm ± 0.003 mm） than in the control group （0.232 mm ± 0.002 mm, t = 4.23, P < 0.01） on day 3, and the significant difference existed till day 8 （all P < 0.01）. Histopathological examination of the ear skin revealed that the epidermal thickness was significantly lower in the experimental group （18.62 μm ± 0.19 μm） than in the control group （27.79 μm ± 1.58 μm, t = 4.35, P < 0.01）. Immunofluorescence staining showed that the degree of neutrophil infiltration in the mouse ear tissue was lower in the experimental group than in the control group. As flow cytometry showed, the proportion of neutrophils was significantly lower in the experimental group （1.57% ± 0.12%） than in the control group （3.03% ± 0.33%, t = 3.31, P = 0.016）. In the ear tissues, the experimental group showed significantly decreased proportion of γδT cells or IL-17+ γδT cells （4.88% ± 0.42%, 40.53% ± 1.76% respectively） compared with the control group （9.45% ± 1.22%, 56.56% ± 0.66% respectively; t = 2.75, 10.27 respectively, both P < 0.05）. In the draining lymph nodes, the experimental group showed significantly increased proportion of γδT cells or IL-17+ γδT cells compared with the control group （t = 5.781, 4.140 respectively, both P < 0.05）, and the fluorescence intensity of S1P1 and CLA in the γδT cells was significantly lower in the experimental group than in the control group （P < 0.05）. Conclusion    FTY720 can alleviate imiquimod-induced psoriasis-like manifestations in mouse models, likely by down-regulating the expression of S1P1 and CLA in γδT cells, increasing the proportion of γδT cells in the draining lymph nodes followed by the decrease of their proportion in the skin, and decreasing the production of IL-17 in skin tissues. 

Key words: Psoriasis, Mice, inbred C57BL, Receptors, antigen, T-cell, gamma-delta, Interleukin-17, Sphingosine-1-phosphate receptors ,