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PD-L2基因敲除小鼠胶原抗体诱导的关节炎模型建立与评价OA

Establishment and evaluation of collagen antibody-induced arthritis model in PD-L2 knockout mice

中文摘要英文摘要

目的:建立PD-L2基因敲除小鼠胶原抗体诱导的关节炎模型(CAIA)并评价小鼠免疫状态.方法:建立野生型(WT)和PD-L2基因敲除(PD-L2-/-)小鼠CAIA模型;测量小鼠体质量和后爪厚度并进行关节炎症评分;HE、Masson和改良番红O-固绿染色评估小鼠关节组织炎症情况;流式细胞术检测两组小鼠脾脏外周T细胞、B细胞、NK细胞和单核-巨噬细胞比例差异,破膜流式检测CD4+T细胞、CD11b+细胞和NK细胞分泌的炎症因子IFN-γ、IL-4和IL-17.结果:WT组和PD-L2-/-组小鼠CAIA模型建立成功.造模后WT-CAIA组和PD-L2-/--CAIA组体质量均减少,后爪厚度增加,关节评分升高.小鼠关节组织病理染色显示PD-L2-/--CAIA组关节肿胀评分、滑膜增厚评分、炎症细胞浸润评分和软骨侵蚀评分低于WT-CAIA组,但差异无统计学意义(P>0.05);脾脏细胞分型发现PD-L2-/--CAIA组CD4+T细胞、CD8+T细胞、CD8+中央记忆T细胞、NK细胞比例低于WT-CAIA组(P<0.05).PD-L2-/--CAIA组CD4+T细胞分泌的IFN-γ和IL-17低于WT-CAIA组(P<0.05),CD11b+细胞分泌的IFN-γ、IL-4和IL-17均低于WT-CAIA组(P<0.05),NK细胞分泌的IFN-γ和IL-17低于WT-CAIA组(P<0.05).结论:PD-L2基因敲除仍能诱导小鼠关节炎发病,但关节组织炎症程度低于WT组.

Objective:To establish a collagen antibody-induced arthritis(CAIA)model of PD-L2 knockout mice and to evalu-ate immune status of mice.Methods:CAIA model of wild-type(WT)and PD-L2 gene knockout(PD-L2-/-)mice were established.Mouse body weight and hind paw thickness were measured and joint scores were performed.HE,Masson and modified saffron-O and fast green staining were used to evaluate inflammation of mouse joint tissues.Flow cytometry was used to detect difference of propor-tions of T cells,B cells,NK cells and monocytes in spleen of two groups,and inflammatory factors IFN-γ,IL-4 and IL-17 secreted by CD4+T cells,CD11b+cells and NK cells were detected by permeabilization flow cytometry.Results:CAIA model of mice in both WT group and PD-L2-/-group were successfully established.After modeling,body weight of WT-CAIA group and PD-L2-/--CAIA group were decreased,thickness of hind paws was increased,and joint score was increased.Joint swelling score,synovial thickening score,inflammatory cell infiltration score and cartilage erosion score in PD-L2-/--CAIA group were lower than WT-CAIA group,but there was no significant difference(P>0.05).Proportions of CD4+T cells,CD8+T cells,CD8+central memory T cells and NK cells in PD-L2-/--CAIA group were lower than WT-CAIA group(P<0.05).Secretion of IFN-γ and IL-17 by CD4+T cells in PD-L2-/--CAIA group were lower than WT-CAIA group(P<0.05),secretion of IFN-γ,IL-4 and IL-17 by CD11b+cells were lower than WT-CAIA group(P<0.05),and secretion of IFN-γ and IL-17 by NK cells were lower than WT-CAIA group(P<0.05).Conclusion:PD-L2 knockout can still induce onset of arthritis of mice,but degree of inflammation of joint tissue is lower than WT group.

宋赛哲;杨艳红;沈宇;刘翠平

苏州大学附属第一医院江苏省临床免疫研究所,苏州 215021南通大学附属医院妇产科,南通 226001苏州大学附属第一医院江苏省临床免疫研究所,苏州 215021苏州大学附属第一医院江苏省临床免疫研究所,苏州 215021

医药卫生

PD-L2胶原抗体诱导的关节炎模型

PD-L2Collagen antibody-induced arthritisModel

《中国免疫学杂志》 2026 (6)

1306-1311,6

苏州市姑苏卫生人才计划培养项目(GSWS2020011)苏州市科技计划项目(SKY2023138).

10.3969/j.issn.1000-484X.2026.06.005

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