The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, People's Republic of China.
University Eye Clinic Maastricht, Maastricht, Netherlands.
Graefes Arch Clin Exp Ophthalmol. 2021 Apr;259(4):987-998. doi: 10.1007/s00417-020-04972-6. Epub 2020 Oct 20.
Increased linoleic acid (LA) was observed in acute anterior uveitis (AAU) patient feces in our previous study. To investigate the immunoregulatory effect of LA, we studied the effect of LA on human and murine dendritic cells (DCs), CD4T cells, and retinal pigment epithelial (RPE) cells in vitro.
The level of LA in feces from AAU patients and healthy individuals was measured by gas chromatography coupled with a mass spectrometer (GC-MS). The immunoregulatory effect of LA on human and murine DCs, CD4 T cells, and RPE cells was evaluated by enzyme linked immunosorbent assay (ELISA) and flow cytometry (FCM). The effect of LA on DCs was evaluated by Tandem mass tag (TMT)-based proteomics analysis.
Increased LA was observed in feces from AAU patients (1018.35 ± 900.01 mg/kg) as compared with healthy individuals (472.55 ± 365.49 mg/kg, p = 0.0136). LA attenuated the antigen-presenting function of human and murine DCs by decreasing the expression of CD40, the secretion of IL-6 and IL-12p70, and the ability to shift naïve T cells towards T helper type 1 (Th1) and Th17 cells. LA also inhibited the secretion of MCP-1 and IL-8 from RPE cells. Proteomics analysis showed differential expression of 28 proteins, including squalene epoxidase (SQLE), farnesyl-diphosphate farnesyltransferase 1 (FDFT1), and cytochrome P450 family 51 subfamily A member 1 (CYP51A1), in LA-treated DCs compared with controls. LA also accelerated the apoptosis of DCs from healthy individuals.
LA inhibited the function of human and murine DCs, CD4T cells, and RPE cells, regulated the expression of proteins, and promoted the apoptosis of human DCs. These results collectively suggest that LA might decrease the function of immune cells in vitro, and further studies are needed to investigate its role in the pathogenesis of AAU.
在我们之前的研究中，观察到急性前葡萄膜炎（AAU）患者粪便中花生四烯酸（LA）增加。为了研究 LA 的免疫调节作用，我们研究了 LA 对人源和鼠源树突状细胞（DC）、CD4T 细胞和视网膜色素上皮（RPE）细胞的体外作用。
通过气相色谱-质谱联用（GC-MS）测量 AAU 患者和健康个体粪便中 LA 的水平。通过酶联免疫吸附测定（ELISA）和流式细胞术（FCM）评估 LA 对人源和鼠源 DC、CD4T 细胞和 RPE 细胞的免疫调节作用。通过串联质谱标签（TMT）蛋白质组学分析评估 LA 对 DC 的作用。
与健康个体（472.55 ± 365.49 mg/kg）相比，AAU 患者粪便中 LA 水平升高（1018.35 ± 900.01 mg/kg，p = 0.0136）。LA 通过降低 CD40 的表达、减少 IL-6 和 IL-12p70 的分泌以及减弱将初始 T 细胞向 Th1 和 Th17 细胞分化的能力，抑制人源和鼠源 DC 的抗原呈递功能。LA 还抑制 RPE 细胞分泌单核细胞趋化蛋白 1（MCP-1）和白细胞介素 8（IL-8）。蛋白质组学分析显示，与对照组相比，LA 处理后的 DC 中 28 种蛋白的表达存在差异，包括角鲨烯环氧化酶（SQLE）、法呢基二磷酸法呢基转移酶 1（FDFT1）和细胞色素 P450 家族 51 亚家族 A 成员 1（CYP51A1）。LA 还加速了健康个体来源的 DC 凋亡。
LA 抑制人源和鼠源 DC、CD4T 细胞和 RPE 细胞的功能，调节蛋白表达，并促进人源 DC 的凋亡。这些结果共同表明，LA 可能在体外降低免疫细胞的功能，进一步的研究需要探讨其在 AAU 发病机制中的作用。
