The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, PR China.
University Eye Clinic Maastricht, Maastricht, Limburg, the Netherlands.
Int Immunopharmacol. 2020 Apr;81:106270. doi: 10.1016/j.intimp.2020.106270. Epub 2020 Feb 7.
Berberine (BBR) was reported to have immunoregulatory and anti-inflammatory properties. In this study, we investigated whether BBR could exert its effects on the development of experimental autoimmune uveitis (EAU), and if so, what was the underlying mechanism?
EAU was induced in B10R.III mice by immunization with IRBP 161-180, followed by 100 mg/kg/d BBR intragastric administration. Disease severity was assessed by evaluation of clinical and histopathological scores. Blood-retinal barrier (BRB) breakdown was tested by Evans blue. Effector and regulatory T (Treg) cell balance was evaluated by quantitative real-time PCR and flow cytometry. Spleen transcriptome was characterized by RNA sequencing (RNA-seq). Gut microbiota composition was investigated by 16S rRNA analysis.
BBR treatment significantly blocked EAU as shown by the decrease of the clinical and histological scores, as well as the inhibition of BRB breakdown. The frequency of splenic Th1 and Th17 cells was decreased, whereas Treg cells were increased in the BBR-treated group. RNA-seq of the spleen revealed 476 differentially expressed genes (DEGs) between the EAU and EAU-BBR group. GO functional classification, as well as KEGG analysis demonstrated that BBR treatment markedly influences genes belonging to chromatin remodeling and immune-related pathways. Intervention with BBR modified the gut microbiome in EAU mice, increasing the number of bacteria with immunomodulatory capacity. Depletion of gut microbiota affected the efficacy of BBR on EAU. Moreover, the altered bacterial strains showed a significant correlation with the expression of histones.
BBR inhibited IRBP induced EAU, which was associated with a significant change in the spleen transcriptome and intestinal microbial composition.
小檗碱（BBR）具有免疫调节和抗炎作用。在这项研究中，我们研究了 BBR 是否可以对实验性自身免疫性葡萄膜炎（EAU）的发展发挥作用，如果可以，其作用机制是什么？
通过用 IRBP 161-180 免疫接种诱导 B10R.III 小鼠发生 EAU，随后给予 100mg/kg/d 的 BBR 灌胃给药。通过评估临床和组织病理学评分来评估疾病严重程度。通过 Evans 蓝检测血视网膜屏障（BRB）的破坏。通过定量实时 PCR 和流式细胞术评估效应和调节性 T（Treg）细胞平衡。通过 RNA 测序（RNA-seq）表征脾脏转录组。通过 16S rRNA 分析研究肠道微生物群组成。
BBR 治疗显著阻断了 EAU，表现为临床和组织病理学评分降低，以及 BRB 破坏的抑制。BBR 治疗组脾脏中 Th1 和 Th17 细胞的频率降低，而 Treg 细胞的频率增加。脾脏的 RNA-seq 显示 EAU 和 EAU-BBR 组之间有 476 个差异表达基因（DEG）。GO 功能分类和 KEGG 分析表明，BBR 处理显著影响属于染色质重塑和免疫相关途径的基因。BBR 干预改变了 EAU 小鼠的肠道微生物群，增加了具有免疫调节能力的细菌数量。肠道微生物群的耗竭影响了 BBR 对 EAU 的疗效。此外，改变的细菌菌株与组蛋白的表达呈显著相关性。
BBR 抑制了 IRBP 诱导的 EAU，这与脾脏转录组和肠道微生物组成的显著变化有关。
