Fine particulate matter potentiates Th17-cell pathogenicity in experimental autoimmune uveitis via ferroptosis

作者：Yaning Liu, Wanyun Zhang, Hongmiao Wang, Hui Liu, Qiuyue Yu, Xiang Luo, Xiaojie Feng, Peizeng Yang · 发表于：Ecotoxicology and Environmental Safety · 年份：2024 · DOI：10.1016/j.ecoenv.2024.116979 · 被引用次数：8 · 研究领域：Extracellular vesicles in disease、Ocular Diseases and Behçet’s Syndrome、Systemic Lupus Erythematosus Research

The effect of fine particulate matter (PM2.5) on the development of uveitis remains unclear. Therefore, this study was designed to investigate the role of PM2.5 in experimental autoimmune uveitis (EAU) and its potential mechanism. Our results showed that PM2.5 could exacerbate the activity of EAU, as evidenced by severer clinical and pathological changes, correlated with elevated Th17 cells frequency and IL-17A expression. Proteomic analysis revealed ferroptosis was the most significant pathway. In vivo, the levels of Fe 2+ , ROS, lipid ROS, and malondialdehyde, as well as the expression of TFRC, HMOX1, FTH1, and FTL1 in CD4 + T cells were increased, while GSH/GSSG ratio and the expression of ACSL1 and GPX4 were decreased after PM2.5 exposure. In vitro, the expression of TFRC and HMOX1 were increased, while the expression FTH1, FTL1, ACSL1, and GPX4 were decreased after PM2.5 exposure. Ferrostatin-1 effectively alleviated PM2.5-induced intraocular inflammation and suppressed the frequency of Th17 cells. These results suggest that PM2.5 could aggravate intraocular inflammation and immune response in EAU mice through ferroptosis. Ferroptosis could be a potential marker for the prevention and treatment of uveitis. • PM2.5 aggravated intraocular inflammation of experimental autoimmune uveitis mice. • PM2.5 promoted Th17 cells differentiation in experimental autoimmune uveitis mice. • PM2.5 induced iron overload and oxidative stress in CD4 + T cells. • Inhibiting ferroptosis can a...