Xinyue Huang1, Shenglan Yi1, Jianping Hu1, Ziyu Du1, Qingfeng Wang1, Zi Ye1, Guannan Su1, Aize Kijlstra2, Peizeng Yang3. 1. The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, People's Republic of China. 2. University Eye Clinic Maastricht, Maastricht, Netherlands. 3. The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, People's Republic of China. peizengycmu@126.com.
Abstract
PURPOSE: 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), CD4+T cells, and retinal pigment epithelial (RPE) cells in vitro. METHODS: 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. RESULTS: 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. CONCLUSION: LA inhibited the function of human and murine DCs, CD4+T 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.
PURPOSE: 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), CD4+T cells, and retinal pigment epithelial (RPE) cells in vitro. METHODS: The level of LA in feces from AAUpatients 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. RESULTS: Increased LA was observed in feces from AAUpatients (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. CONCLUSION: LA inhibited the function of human and murine DCs, CD4+T 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.