TRIM21 通过泛素化口腔扁平苔藓 T 细胞中的 NF-κB 促进炎症。
TRIM21 promotes inflammation by ubiquitylating NF-κB in T cells of oral lichen planus.
机构信息
Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.
出版信息
J Oral Pathol Med. 2023 May;52(5):448-455. doi: 10.1111/jop.13428. Epub 2023 Mar 28.
BACKGROUND
Oral lichen planus (OLP) is a mucocutaneous inflammatory disease affecting 1% general population. Tripartite motif-containing protein 21 (TRIM21) shows a significant role in OLP. This study aimed to explore the function and mechanism of TRIM21 in T cells of OLP.
METHODS
Differential gene expression profile in OLP versus healthy controls (HCs) was constructed by RNA sequencing. Protein expression level and infiltration sites of TRIM21 in OLP were detected by immunoblot, immunohistochemistry, and immunofluorescence. Expression of proinflammatory cytokines and chemokines including IL-6, TNF-α, ICAM1, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3 TRIM21 T cells were measured by quantitative real-time polymerase chain reaction analysis. Downstream pathways and substrates of TRIM21 were explored by immunoblot and immunoprecipitation. Whether TRIM21 ubiquitination its substrate and ubiquitination form were tested by ubiquitination assay in vitro.
RESULTS
Compared with HCs, TRIM21 exhibited a higher level in OLP, which expressed mainly in CD3 T lymphocytes in OLP tissues. Overexpressed TRIM21 enhanced the expression of IL-6, TNF-α, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3 T cell line through ubiquitinating nuclear factor-κB (NF-κB) via a lysine 63 (K63) linkage, which eventually activating NF-κB signaling pathway.
CONCLUSIONS
In OLP, TRIM21 promoted inflammation through ubiquitylating NF-κB and activating NF-κB signaling pathway.
背景
口腔扁平苔藓（OLP）是一种影响 1%普通人群的黏膜皮肤炎症性疾病。三结构域蛋白 21（TRIM21）在 OLP 中表现出重要作用。本研究旨在探讨 TRIM21 在 OLP 中的 T 细胞中的功能和作用机制。
方法
通过 RNA 测序构建 OLP 与健康对照（HC）之间的差异基因表达谱。通过免疫印迹、免疫组织化学和免疫荧光检测 TRIM21 在 OLP 中的蛋白表达水平和浸润部位。通过定量实时聚合酶链反应分析检测 CD3 TRIM21 T 细胞中包括 IL-6、TNF-α、ICAM1、CXCL1、CXCL8、CXCL9 和 CXCL11 在内的促炎细胞因子和趋化因子的表达。通过免疫印迹和免疫沉淀探索 TRIM21 的下游途径和底物。通过体外泛素化测定试验测试 TRIM21 是否泛素化其底物及其泛素化形式。
结果
与 HCs 相比，TRIM21 在 OLP 中表达水平较高，主要在 OLP 组织中的 CD3 T 淋巴细胞中表达。过表达的 TRIM21 通过赖氨酸 63（K63）连接泛素化核因子-κB（NF-κB），从而增强 CD3 T 细胞系中 IL-6、TNF-α、CXCL1、CXCL8、CXCL9 和 CXCL11 的表达，最终激活 NF-κB 信号通路。
结论
在 OLP 中，TRIM21 通过泛素化 NF-κB 并激活 NF-κB 信号通路促进炎症。
Zotero 插件