抗CD122抗体对小鼠银屑病样皮损的影响及其作用机制

doi:10.3760/cma.j.issn.1007-1245.2024.02.015

摘要/Abstract

摘要：

目的　探讨抗CD122抗体对小鼠银屑病样皮损的影响及其作用机制。方法　研究时间为2020年7月1日至11月23日。选用56只BALB/c雌性小鼠随机分配为4组：凡士林对照组（空白对照组）、咪喹莫特模型组（模型组）、同型对照抗体实验组（实验组A）、抗CD122抗体实验组（实验组B）。采用银屑病面积与严重程度指数（PASI）评分观察银屑病样皮损动态变化；显微镜下观察皮损组织病理改变，并测量表皮层厚度；采用免疫荧光双标法检测皮损中T_RM细胞的表型及变化；免疫组织化学法检测皮损中白细胞介素-15（IL-15）、白细胞介素-17A（IL-17A）的表达及变化。计量资料采用独立样本t检验。结果　免疫荧光双标显示，模型组初次（3 d、6 d）T_RM细胞数量CD3⁺CD103⁺［（16.40±1.43）细胞个数/视野、（29.80±2.28）细胞个数/视野］、CD4⁺CD103⁺［（10.80±1.77）细胞个数/视野、（16.20±1.28）细胞个数/视野］、CD8⁺CD103⁺［（15.10±1.65）细胞个数/视野、（26.05±1.43）细胞个数/视野］、CD122⁺CD103⁺ ［（16.52±1.43）细胞个数/视野、（26.80±1.40）细胞个数/视野］均高于对照组（均P<0.01）；实验组B初次（3 d、6 d）及再次（38 d、41 d）刺激皮损中T_RM细胞数量均低于同一时间模型组、实验组A（均P<0.05），以CD8⁺T_RM细胞降低为主（P<0.01）。免疫组织化学结果显示，模型组再次（38 d、41 d）皮损中IL-15、IL-17A的表达［（115.66±3.69）IOD/area、（121.65±3.36）IOD/area及（104.30±3.47）IOD/area、（59.87±3.20）IOD/area］均高于对照组［（28.15±2.25）IOD/area、（28.05±2.15）IOD/area及（25.63±2.10）IOD/area、（25.01±2.71）IOD/area］，差异均有统计学意义（均P<0.05）；实验组B初次（3 d、6 d）及再次（38 d、41 d）刺激皮损中IL-15、IL-17A的表达均低于同一时间模型组和实验组A（均P<0.05）。结论　T_RM细胞、IL-15、IL-17A可能参与小鼠银屑病样皮损的发生和发展，抗CD122抗体可以改善小鼠的银屑病样皮损，该作用可能与其抑制T_RM细胞的形成和功能（以CD8⁺T_RM细胞为主），以及降低IL-15、IL-17A的表达有关。

关键词:

银屑病, CD122, T_RM细胞, IL-15, IL-17A, 动物实验

Abstract:

Objective　To explore the effect and mechanism of anti-CD122 antibody on psoriasis-like skin lesions in mice. Methods　The study was conducted from July 1 to November 23, 2020. A total of 56 BALB/c female mice were randomly assigned to four groups: a vaseline control group (blank control group), an imiquimod model group (model group), an isotype control antibody experimental group (experimental group A), and an anti-CD122 antibody experimental group (experimental group B). The dynamic changes of psoriasis-like skin lesions were observed using the Psoriasis Area and Severity Index (PASI) score; the pathological changes of skin lesion tissues were observed under the microscope and the thickness of the epidermal layer was measured; the phenotypes and changes of T_RM cells in skin lesions were detected using the immunofluorescence double-labeling method; the expressions and changes of interleukin (IL)-15 and IL-17A in skin lesions were detected using the immunohistochemical method. Independent sample t test was used for the measurement data. Results　The immunofluorescence double-labeling showed that the number of T_RM cells in the initial lesions (3 and 6 days) of the model group [CD3⁺CD103⁺: (16.40±1.43) cell count/field of view, (29.80±2.28) cell count/field of view; CD4⁺CD103⁺: (10.80±1.77) cell count/field of view, (16.20±1.28) cell count/field of view; CD8⁺CD103⁺: (15.10±1.65) cell count/field of view, (26.05±1.43) cell count/field of view; CD122⁺CD103⁺: (16.52±1.43) cell count/field of view, (26.80±1.40) cell count/field of view] were higher than those in control group (all P<0.01). The number of T_RM cells in the initial (3 and 6 days) and re-stimulated (38 and 41 days) lesions of the experimental group B were lower than those in the model group and the experimental group A at the same time (all P<0.05), with CD8⁺ T_RM cells predominantly reduced (P<0.01). The immunohistochemical results showed that the expressions of IL-15 and IL-17A in the initial lesions (38 and 41 days) of the model group [(115.66±3.69) IOD/area, (121.65±3.36) IOD/area, (104.30±3.47) IOD/area, and (59.87±3.20) IOD/area] were higher than those of the control group [(28.15±2.25) IOD/area, (28.05±2.15) IOD/area, (25.63±2.10) IOD/area, and (25.01±2.71) IOD/area], with statistically significant differences (all P<0.05). The expressions of IL-15 and IL-17A in the initial (3 and 6 days) and re-stimulated (38 and 41 days) lesions of the experimental group B were lower than those of the model group and experimental group A at the same time (all P<0.05). Conclusions　T_RMcells, IL-15, and IL-17A might be involved in the occurrence and development of psoriasis-like skin lesions in mice. Anti-CD122 antibody can improve psoriasis-like lesions in mice, and this effect might be related to its inhibition of formation and function of T_RM cells, mainly CD8⁺T_RM cells, as well as the reduction of IL-15 and IL-17A expressions.

Key words:

Psoriasis, CD122, Tissue resident memory T cells, Interleukin-15, Interleukin-17A, Animal experiment

李华润温炬郑荣昌周玉婵秦思李婷黄锦萍.

抗CD122抗体对小鼠银屑病样皮损的影响及其作用机制 [J]. 国际医药卫生导报, 2024, 30(2): 249-257.

Li Huarun, Wen Ju, Zheng Rongchang, Zhou Yuchan, Qin Si, Li Ting, Huang Jinping.

Effect and mechanism of anti-CD122 antibody on psoriasis-like skin lesions in mice [J]. International Medicine and Health Guidance News, 2024, 30(2): 249-257.

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