The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, PR China.
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, PR China.
Clin Immunol. 2022 Jul;240:109056. doi: 10.1016/j.clim.2022.109056. Epub 2022 May 31.
Aberrant lipid metabolism plays a role in inflammation and progression of autoimmune diseases but the definite mechanism remains unclear. In this study we investigate lipidomic profiles in Behçet's disease (BD) and the role of triglyceride (TAG) in the pathogenesis of autoimmune uveitis. Lipidomics revealed a distinct lipid metabolite profile including increased TAG metabolites in plasma of active BD patients. TAG could stimulate the proliferation, IL-17 and IFN-γ expression by CD4 T cells and Th1, Th17 cell differentiation in vitro, but did not influence neutrophils. A922500 inhibited the TAG generation, ameliorated the EAU severity, decreased Th17 frequency and IL-17 expression by CD4 T cells in vivo. The proteomocis analysis showed an up-regulation of apoptosis-related protein, Pik3r2, in CD4 T cells from A922500-treated mice. In conclusion, TAG can stimulate human CD4 T cells and the inhibition of its generation could significantly ameliorate EAU activity in association with down-regulated Th17 cell response.
异常的脂质代谢在炎症和自身免疫性疾病的进展中起作用，但确切的机制尚不清楚。在这项研究中，我们研究了白塞病（BD）的脂质组学特征以及甘油三酯（TAG）在自身免疫性葡萄膜炎发病机制中的作用。脂质组学揭示了一种独特的脂质代谢物谱，包括活性 BD 患者血浆中 TAG 代谢物的增加。TAG 可刺激 CD4 T 细胞的增殖、IL-17 和 IFN-γ表达以及体外 Th1、Th17 细胞分化，但不影响中性粒细胞。A922500 可抑制 TAG 的产生，改善 EAU 的严重程度，降低体内 CD4 T 细胞中 Th17 频率和 IL-17 的表达。蛋白质组学分析显示，A922500 处理的 CD4 T 细胞中凋亡相关蛋白 Pik3r2 的表达上调。总之，TAG 可刺激人 CD4 T 细胞，其生成的抑制可显著改善 EAU 的活性，同时下调 Th17 细胞的反应。
