Ryu Hye-Myung, Islam S M Shamsul, Sayeed Hasan M, Babita Rahar, Seong Je Kyung, Lee Ho, Sohn Seonghyang
Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Department of Biomedical Sciences, Ajou University, Suwon 16499, Republic of Korea.
Clin Immunol. 2023 May;250:109305. doi: 10.1016/j.clim.2023.109305. Epub 2023 Mar 31.
Behçet's disease (BD) is a chronic multisystem inflammatory disorder. Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphism has been reported as a risk factor for BD. However, the immunological role of ERAP1 in BD remains unclear. Therefore, the purpose of this study was to investigate the immunological role of ERAP1 in BD using a mouse model. ERAP1 incomplete expressing mice (ERAP1 hetero, +/-) were generated and inoculated with herpes simplex virus 1 to produce a BD mouse model. In these mice, dendritic cell activation markers and other immune response-related markers were analyzed. Among them, the factor showing a significant difference between ERAP1+/- BD mice and WT BD mice was IL-17. In ERAP1+/-, BD had significantly different expression levels of CD80, CD11b, Ly6G, RORγt, IFNγ, and IL-17 compared to asymptomatic controls. This study demonstrates ERAP1 defective expressions play an important role in BD development through inappropriate regulation of Th17.
白塞病（BD）是一种慢性多系统炎症性疾病。内质网氨肽酶1（ERAP1）基因多态性已被报道为BD的一个危险因素。然而，ERAP1在BD中的免疫作用仍不清楚。因此，本研究的目的是使用小鼠模型研究ERAP1在BD中的免疫作用。构建了ERAP1不完全表达小鼠（ERAP1杂合子，+/-），并用1型单纯疱疹病毒接种以建立BD小鼠模型。对这些小鼠的树突状细胞激活标志物和其他免疫反应相关标志物进行了分析。其中，在ERAP1+/- BD小鼠和野生型BD小鼠之间显示出显著差异的因子是IL-17。与无症状对照组相比，在ERAP1+/-小鼠中，BD的CD80、CD11b、Ly6G、RORγt、IFNγ和IL-17表达水平存在显著差异。本研究表明，ERAP1缺陷表达通过对Th17的不适当调节在BD的发展中起重要作用。
