恶唑酮诱导的小鼠急性至慢性皮炎T细胞免疫表型的变化

Changes in T Cell Immunophenotypes in Oxazolone-Induced Acute to Chronic Allergic Dermatitis in Mice

目的比较恶唑酮诱发的急性至慢性皮炎小鼠皮损处T细胞免疫表型的变化。方法建立恶唑酮(oxazolone,OX)诱导的急性、亚急性和慢性皮炎小鼠模型。通过小鼠耳部皮损及组织学改变、T细胞极化相关转录因子及效应细胞因子表达、角质细胞来源的细胞因子表达和血清IgE水平等比较半抗原诱导的急性至慢性皮炎小鼠模型皮损处T细胞免疫表型的变化。结果随着OX激发次数的增加,小鼠皮肤厚度呈逐渐增加然后缓慢下降并趋于稳定的趋势。急性至慢性皮炎小鼠外周血清IgE水平均显著升高,在亚急性期达最高水平。OX诱导的急性皮炎,皮损处Th1效应细胞因子IFN-γ和TNF-α表达显著升高;OX诱导的亚急性皮炎,皮损处Th2效应细胞因子IL-4和IL-13表达开始显著升高,并出现IL-22的升高;OX诱导的慢性皮炎,皮损处Th17效应细胞因子显著升高。角质形成细胞来源的IL-25和IL-33在急性皮炎中表达最高,之后逐渐下降,胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)表达水平在炎症各阶段无变化;IL-36α在亚急性皮损中升高并持续升高至慢性期;IL-1β和IL-6在亚急性和慢性皮损中显著升高。结论增加恶唑酮激发次数可逐渐诱导小鼠急性、亚急性和慢性皮炎改变,在此过程中皮损内T细胞表型也表现为从Th1向Th2优势转化,再向Th1、Th2和Th17混合表型的变化。

Objective To compare the changes in T cell immunophenotype in the skin lesions of mice with acute to chronic dermatitis induced by oxazolone(OX).Methods Acute,subacute and chronic dermatitis mouse models induced by OX were established.The changes of T cell immunophenotypes in the skin lesions of mouse models of acute to chronic dermatitis induced by haptens were compared by the gross and histological changes of mouse ear lesions,the expression of T cell polarization-related transcription factors and effector cytokines,keratinocyte-derived cytokines and serum IgE levels.Results With the increase of the number of OX stimulation,the skin thickness of mice gradually increased and then slowly decreased and tended to stabilize.The peripheral serum IgE level of mice with acute to chronic dermatitis increased significantly,reaching the highest level in the subacute phase.In acute dermatitis induced by OX,the expression of Th1 effector cytokines IFN-γand TNF-αwas significantly increased in the skin lesions.In OX-induced subacute dermatitis,the expression of Th2 effector cytokines IL-4 and IL-13 in the skin lesions began to increase significantly,and the expression level of IL-22 increased.In OX-induced chronic dermatitis,Th17 effector cytokines were significantly increased in the skin lesions.The expression of IL-25 and IL-33 derived from keratinocytes was the highest in acute dermatitis,and then gradually decreased.Thymic stromal lymphopoietin(TSLP)expression level did not change at all stages of inflammation.IL-36αincreased in subacute skin lesions and continued to increase in chronic stage;IL-1βand IL-6 were significantly elevated in subacute and chronic skin lesions.Conclusion Increasing the times of OX stimulation can gradually induce acute,subacute and chronic dermatitis changes in mice.In the meantime,the phenotype of T cells in the skin lesions also shows a dominant transformation from Th1 to Th2,and then to a mixed phenotype of Th1,Th2 and Th17.