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Linoleic acid inhibits in vitro function of human and murine dendritic cells, CD4+T cells and retinal pigment epithelial cells

  • Inflammatory Disorders
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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.

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Funding

This study was supported by National Natural Science Foundation Key Program (81930023), Natural Science Foundation Major International (Regional) Joint Research Project (81720108009), Chongqing Outstanding Scientists Project (2019) , Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), Chongqing Science & Technology Platform and Base Construction Program (cstc2014pt-sy10002) and the Chongqing Chief Medical Scientist Project (2018).

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Authors and Affiliations

  1. The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, People’s Republic of China

    Xinyue Huang, Shenglan Yi, Jianping Hu, Ziyu Du, Qingfeng Wang, Zi Ye, Guannan Su & Peizeng Yang

  2. University Eye Clinic Maastricht, Maastricht, Netherlands

    Aize Kijlstra

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  1. Xinyue Huang
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  2. Shenglan Yi
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Correspondence to Peizeng Yang.

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The study adhered to the Declaration of Helsinki and was approved by the First Affiliated Hospital of Chongqing Medical University Ethics Research Committee. Informed consent was obtained from all subjects enrolled.

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Huang, X., Yi, S., Hu, J. et al. Linoleic acid inhibits in vitro function of human and murine dendritic cells, CD4+T cells and retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol 259, 987–998 (2021). https://doi.org/10.1007/s00417-020-04972-6

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