摘要
目的探讨HMGB1-RAGE通路对结肠癌进展过程中炎症微环境的免疫调节作用。方法采用免疫组化SP法检测66例结肠癌和癌旁正常组织中RAGE和FOXP3的表达;采用免疫荧光法检测RAGE和FOXP3在结肠癌组织中的定位并分析两者表达的关系。用免疫磁珠分离小鼠血液初始T细胞,以重组RAGE配体高迁移率族蛋白HMGB1联合TGF-β1刺激初始T细胞分化为调节性T细胞(Treg);利用流式细胞术分析CD4+CD25+FOXP3+Treg细胞的比例在HMGB1刺激后的改变。结果RAGE和FOXP3蛋白表达均在分化低、浸润层次深、有淋巴结转移、TNM分期晚的结肠癌组织中表达增高(P均<0.05);两者在结肠癌组织中过表达,分别占75%和60%,且表达存在明显的共定位。重组HMGB1蛋白联合TGF-β1刺激初始T细胞,可以明显增强TGF-β1诱导的Treg分化(9.16%vs 5.22%),促进体外iTreg数量的增加。结论HMGB1-RAGE通路参与Treg分化的调控,发挥促免疫耐受作用,促进结肠癌的进展。
Purpose To explore the immunomodulatory effect of HMGB1-RAGE pathway on inflammatory microenvironment in the progression of colon cancer.Methods The expressions of RAGE and FOXP3 in 66 cases of colon cancer and its adjacent tissues were detected by immunohistochemical staining,and the results were statistically analyzed.Besides,the expression and relationship of RAGE and FOXP3 in colorectal cancer were detected by immunofluorescence staining.The initial T cells of mouse blood were isolated by immunomagnetic beads,and the initial T cells were stimulated to differentiate into regulatory T cells(Treg)by recombinant RAGE ligand high mobility group protein HMGB1 combined with TGF-β1.The ratio of CD4+CD25+FOXP3+Treg cells was analyzed by flow cytometr after HMGB1 stimulationy.Results The expressions of RAGE and FOXP3 was increased in the colon cancer tissues with poor differentiation,deep infiltration,lymph node metastasis and late TNM stage(P<0.05),and they were overexpressed in 75%and 60%of colon cancer tissues,respectively,with obvious co-location.Recombinant HMGB1 protein combined with TGF-β1 stimulated primary T cells and significantly enhanced TGF-β1-induced Treg differentiation(9.16%vs 5.22%),and promoted the increase of iTreg number in vitro.Conclusion HMGB1-RAGE pathway is involved in the regulation of Treg differentiation,which might contribute to immune tolerance and lead to the progression of colon cancer.
作者
黄建辉
蒋晨
王兴超
钱飞
HUANG Jian-hui;JIANG Chen;WANG Xing-chao;QIAN Fei(Department of Pathology,Affiliated Hospital of Nantong University,Nantong 226001,China;Department of General Surgery,Affiliated Hospital of Nantong University,Nantong 226001,China;Department of Blood Transfusion,Affiliated Hospital of Nantong University,Nantong 226001,China)
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2022年第4期416-420,共5页
Chinese Journal of Clinical and Experimental Pathology
