小桶
自噬
镍过敏
PI3K/AKT/mTOR通路
生物
磷酸化
信号转导
细胞生物学
刺猬信号通路
化学
免疫学
过敏
生物化学
基因表达
接触性皮炎
基因
基因本体论
细胞凋亡
作者
Wei Gong,Tingting Shen,Xueyan Huang,Luo Zhang,Yulong Tan,Guodong He,Zeze Wang,Ping Li,Xiaoqian Liu,Xiaohui Yu,Boyi Zhang,Huan‐Xiang Zhou,Xue Li,Xuesen Yang
标识
DOI:10.1016/j.ecoenv.2022.113878
摘要
Nickel-induced allergic contact dermatitis (ACD) is a common skin disease. The mechanism by which nickel causes ACD is not clear. There is no treatment for it, only symptomatic therapy. However, due to the lifetime sensitization characteristics, the recurrence rate in patients is high. T lymphocytes play a key role in nickel-induced ACD. Elucidating the potential mechanism underlying nickel-induced T lymphocyte signalling might make it possible to achieve targeted treatment of nickel-induced ACD. In our study, a phosphoproteomic approach based on tandem mass tag (TMT) labelling and LCMS/MS analyses was employed. An animal model of nickel allergy was established. Splenic T lymphocytes were purified for quantitative phosphoproteomic analysis. The numbers of phosphoproteins, phosphopeptides and phosphosites identified in this study were 3072, 7977 and 10,200, respectively. Comprehensive gene ontology (GO) analysis combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that nickel can significantly affect the phosphorylation of the mTOR signalling pathway in T lymphocytes. Western blotting analysis was used to detect changes in the expression of autophagy-related proteins (Beclin 1, LC3II, and p62). Nickel allergy changed autophagy-related protein expression (p < 0.05). It has been demonstrated that nickel causes autophagy of T lymphocytes in the spleen. Using autophagy inhibitors to intervene, it was found that Th1 differentiation was inhibited, and the expression of Th1-related inflammatory factors was downregulated. Overall, the identification of relevant signalling pathways yielded new insights into the molecular mechanisms underlying nickel allergy and might help in the discovery and development of mechanism-based drugs.
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