Liu Xiao-Ru, Li Ming, Hao Qian-Qian, Yu Ya-Jie, Liao Cai, Yu Rui, Kong De-Lei, Wang Yun
Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Virulence. 2025 Dec;16(1):2502555. doi: 10.1080/21505594.2025.2502555. Epub 2025 May 12.
Cysteinyl leukotrienes (CysLTs), as potent lipid inflammatory mediators, play a pivotal role in systemic multi-organ inflammation and inter-organ communication through interactions with their receptors (CysLTRs). However, However, the function of CysLT3R is unclear and lacks a network of cross-organ metabolite interactions, and the clinical use of leukotriene receptor antagonists (LTRAs) has certain limitations. This review systematically synthesizes existing evidence and proposes future directions by clarifying receptor subtype specificity, optimizing targeted therapies, exploring CysLTs' applications in neuroimmunology, and elucidating the dual roles of CysLTs in chronic inflammation. It is indicated that CysLTs activate eosinophils, mast cells, and airway tuft cells, driving type 2 immune responses and mucus secretion in the lungs, thereby exacerbating respiratory diseases such as asthma. In the nervous system, CysLTs aggravate neurodegenerative disorders like cerebral ischemia and Alzheimer's disease by disrupting the blood-brain barrier, promoting glial activation, and inducing neuronal damage. In the gut, CysLTs regulate anti-helminth immunity via the tuft cell-ILC2 pathway and collaborate with prostaglandin D2 (PGD2) to modulate bile excretion and mucosal protection. Furthermore, CysLTs mediate communication through the gut-lung and gut-brain axes via metabolites such as succinate, contributing to cross-organ inflammatory regulation. In conclusion, this review highlights the complex roles of CysLTs in chronic inflammation, providing a theoretical foundation for precise intervention in multi-organ inflammatory diseases, which provides a theoretical framework for precision interventions in multi-organ inflammatory diseases and inspires interdisciplinary breakthroughs.
半胱氨酰白三烯（CysLTs）作为强效脂质炎症介质，通过与其受体（CysLTRs）相互作用，在全身多器官炎症和器官间通讯中发挥关键作用。然而，CysLT3R的功能尚不清楚，且缺乏跨器官代谢物相互作用网络，白三烯受体拮抗剂（LTRAs）的临床应用也存在一定局限性。本综述系统整合现有证据，并通过阐明受体亚型特异性、优化靶向治疗、探索CysLTs在神经免疫学中的应用以及阐明CysLTs在慢性炎症中的双重作用，提出未来研究方向。研究表明，CysLTs激活嗜酸性粒细胞、肥大细胞和气道簇状细胞，驱动肺部2型免疫反应和黏液分泌，从而加重哮喘等呼吸系统疾病。在神经系统中，CysLTs通过破坏血脑屏障、促进神经胶质细胞活化和诱导神经元损伤，加重脑缺血和阿尔茨海默病等神经退行性疾病。在肠道中，CysLTs通过簇状细胞-ILC2途径调节抗蠕虫免疫，并与前列腺素D2（PGD2）协同调节胆汁排泄和黏膜保护。此外，CysLTs通过琥珀酸盐等代谢物介导肠道-肺和肠道-脑轴之间的通讯，促进跨器官炎症调节。总之，本综述强调了CysLTs在慢性炎症中的复杂作用，为多器官炎症性疾病的精准干预提供了理论基础，为多器官炎症性疾病的精准干预提供了理论框架，并激发了跨学科突破。
