粉尘螨Derf2蛋白抑制Foxp3对小鼠弥漫大B细胞淋巴瘤的影响

Dust mites Derf2 inhibits Foxp3 protein in mice with diffuse large B-cell lymphoma

探讨粉尘螨重组Derf2蛋白对小鼠Treg及特异性标记Foxp3蛋白的干扰作用,从而为粉尘螨抗原治疗弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)提供基础实验支持。通过免疫组化检测Foxp3蛋白在DLBCL患者淋巴结石蜡标本中的表达,利用临床数据对Foxp3蛋白在DLBCL的表达与预后情况进行分析。提取粉尘螨重组Derf2蛋白对A20细胞进行干预,检测A20细胞内Foxp3蛋白表达及对细胞增殖能力的影响。建立小鼠DLBCL成瘤动物模型,对模型鼠注射粉尘螨相关抗原,对比各组动物模型的成瘤时间、成瘤速度及成瘤体积。结果显示,免疫组化检测Foxp3蛋白在DLBCL中的表达,发现瘤组织中Foxp3蛋白表达高于瘤旁组织(P<0.05),通过与DLBCL患者临床病理学特征之间关系的分析,得出瘤组织内Foxp3蛋白的高表达是患者预后不良的因素。注射了粉尘螨抗原的小鼠成瘤速度及体积明显下降(P<0.05),瘤内Foxp3蛋白表达较未注射Derf2减少(P<0.05)。这表明Foxp3蛋白在DLBCL患者体内高表达为预后不良因素之一,粉尘螨Derf2对肿瘤Foxp3蛋白的表达能起干扰作用,并抑制体内肿瘤的生长。

We aimed to study the effect of dust mite antigen Derf2 protein on Treg cells and the specific marker Foxp3 protein in mice,so as to provide basic experimental support for dust mite antigen in the treatment of diffuse large B-cell lymphoma（DLBCL）.Immunohistochemistry method was used to detect the expression of Foxp3 protein in paraffin specimen of patients with DLBCL,and clinical data were adopted to analyze the expression of Foxp3 protein in DLBCL and the conditions of prognosis.Dust mites extracted Derf2 protein was used to intervene A20 cells and the expression of Foxp3 protein in cells and its effect on cell reproductive capacity were detected.Mice DLBCL tumor animal models were established,and dust mites associated Derf2 antigens were injected into model mice,the time,rate and volume of tumor growth among various groups of animal models were compared.After immunohistochemistry method was used to detect the expression of Foxp3 protein in DLBCL,it was found that Foxp3 protein expression level was higher in tumor tissues than in adjacent tissues（P 0.05）.Through the analysis of relations between Foxp3 and clinic pathologic features of patients with DLBCL,we found that the high expression of Foxp3 protein in tumor tissues was the factor of patients＇ adverse prognosis.The rate and volume of tumor growth in mice injected with dust mite Derf2 antigen were significantly decreased（P 0.05）,and Foxp3 protein expression in tumor was less than that in control mice（P 0.05）.These findings suggest that high expression of Foxp3 protein in DLBCL is one of the factors of poor prognosis,and the dust mite Derf2 can reduce Foxp3 protein level in tumor and inhibits the growth of tumor in vivo.