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[1]来佳丹,魏诗瑶,李常颖.肾癌来源的IL4I1介导Treg诱导与募集的实验研究[J].天津医科大学学报,2023,29(03):302-308.
　LAI Jia-dan,WEI Shi-yao,LI Chang-ying.Research on inducement and recruitment of Treg mediated by IL4I1 derived from renal cell carcinoma[J].Journal of Tianjin Medical University,2023,29(03):302-308.
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肾癌来源的IL4I1介导Treg诱导与募集的实验研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
29卷
期数:
2023年03期
页码:
302-308
栏目:
临床医学
出版日期:
2023-05-20

文章信息/Info

Title:
Research on inducement and recruitment of Treg mediated by IL4I1 derived from renal cell carcinoma
文章编号:
1006－8147（2023）03-0302-07
作者:
来佳丹; 魏诗瑶; 李常颖
（天津医科大学第二医院泌尿外科，天津市泌尿外科研究所，天津300211）
Author(s):
LAI Jia-dan; WEI Shi-yao; LI Chang-ying
（Department of Urology，Tianjin Institute of Urology，The Second Hospital，Tianjin Medical University，Tianjin 300211，China ）
关键词:
IL4I1; 肾透明细胞癌; 调节性T细胞; 趋化因子
Keywords:
IL4I1;  clear cell renal cell carcinoma;  regulatory T cell;  chemokines
分类号:
R737.1
DOI:
-
文献标志码:
A
摘要:
目的：探讨肾癌细胞来源的白细胞介素4诱导蛋白1（IL4I1）对调节性T细胞（Treg）的诱导与募集作用。方法：利用公共数据库分析肾透明细胞癌（ccRCC）组织中IL4I1表达与Treg浸润的关系，通过免疫组织化学法（IHC）进行验证；构建稳定敲低IL4I1的786-O细胞系，进行转录组测序（RNA-Seq）及基因集富集分析（GSEA）；实时荧光定量PCR（qPCR）和酶联免疫吸附试验（ELISA）比较敲低786-O细胞系IL4I1表达后肾癌细胞表达趋化因子的变化，流式细胞术（FCM）分析体外IL4I1对Treg诱导分化的影响。结果：IL4I1在ccRCC组织中过表达（t=6.029，P<0.05），并且随着IL4I1表达的升高，肿瘤组织中Treg数量增加（F=13.69，P<0.05）。GSEA显示，沉默IL4I1表达的786-O细胞系和对照细胞系的差异表达谱在细胞因子和趋化因子产生及负向调节其产生的生物学过程（BP）中富集（P. adjust =9.2×10-4、7.5×10-4、7.7×10-4、2.67×10-2）。敲低IL4I1表达后，786-O细胞表达的CC趋化因子配体（CCL）3、CCL4、CCL5、CCL8、CCL17、CCL19在mRNA水平显著下调（t=6.250、7.716、20.640、5.324、6.360、3.484，均P<0.05），同时细胞培养上清中CCL4、CCL5浓度降低（t=6.773、13.64，均P<0.05）。与敲低表达IL4I1细胞共培养的外周血单个核细胞中Treg比例少于对照组（t=3.843，P<0.05）。结论：肾癌组织中IL4I1与Treg浸润密切相关，可能通过调控趋化因子的表达参与Treg在肿瘤局部的募集；肾癌细胞来源的IL4I1能够促进Treg的分化。
Abstract:
Objective： To explore the role of interleukin-4-induced-1 （IL4I1） in inducement and recruitment of regulatory T cells（Treg） in renal cell carcinoma. Methods：The relationship between IL4I1 expression and Tregs infiltration in clear cell renal cell carcinoma（ccRCC） tissues were analyzed by public database. Immunohistochemistry（IHC） was used to verify. A stable IL4I1 knockdown 786-O cell line was established，and RNA-Sequencing（RNA-Seq） and gene set enrichment analysis（GSEA） was performed. Quantitative real-time polymerase chain reaction（qPCR） and enzyme-linked immunosorbent assay（ELISA）were used to observe the expression changes of chemokines in renal cancer cells after knockdown of IL4I1 expression. Flow cytometry（FCM） was used to analyze the influence of IL4I1 on Treg inducement in vitro. Results：IL4I1 was over-expressed in ccRCC tissues（t=6.029，P<0.05）. The number of regulatory T cells in tumor tissues increased with the increase of IL4I1 expression（F=13.69，P<0.05）. Gene set enrichment analysis（GESA） revealed that transcript differential expression of IL4I1-silenced 786-O cells and control cells were enriched in biological process（BP） of cytokine and chemokine production and negative regulation of their production（P. adjust =9.2×10-4，7.5×10-4，7.7×10-4，2.67×10-2）. After IL4I1 was knocked down，the expression of CCL3，CCL4，CCL5，CCL8，CCL17 and CCL19 in 786-O cells were significantly down-regulated at mRNA level（t=6.250，7.716，20.640，5.324，6.360，3.484，all P<0.05），and the concentration of CCL4 and CCL5 in the supernatant decreased（t=6.773，13.64，both P<0.05）. The proportion of Tregs in peripheral blood mononuclear cells co-cultured with IL4I1 knockdown tumor cells was less than that in control group（t=3.843，P<0.05）. Conclusion：In renal cancer tissue，IL4I1 expression is closely related to Treg infiltration. It may possibly play a role in the recruitment of Tregs at tumor area by regulating chemokine expression. IL4I1 derived from renal cancer cells can promote the differentiation of Treg.

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备注/Memo

备注/Memo:
基金项目 天津医科大学第二医院重点实验室基金（ZDSYS202308）
作者简介 来佳丹（1997-），女，硕士在读，研究方向：泌尿系统肿瘤微环境；通信作者：李常颖，E-mail：cli_cvrl@tmu.edu.cn。
更新日期/Last Update: 1900-01-01