Lee Minkyu, Boyce Joshua A, Barrett Nora A
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Jeff and Penny Vinik Center for Translational Immunology Research, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA; email:
Annu Rev Pathol. 2025 Jan;20(1):115-141. doi: 10.1146/annurev-pathmechdis-111523-023509. Epub 2025 Jan 2.
The cysteinyl leukotrienes (CysLTs), LTC, LTD, and LTE, are potent lipid mediators derived from arachidonic acid through the 5-lipoxygenase pathway. These mediators produce both inflammation and bronchoconstriction through three distinct G protein-coupled receptors (GPCRs)-CysLT, CysLT, and OXGR1 (also known as CysLT or GPR99). While CysLT-mediated functions in the effector phase of allergic inflammation and asthma have been established for some time, recent work has demonstrated novel roles for these mediators and their receptors in the induction and amplification of type 2 inflammation. Additionally, in vitro studies and murine models have uncovered diverse regulatory mechanisms that restrain or amplify CysLT receptor activation and CysLT receptor function. This review provides an overview of CysLT biosynthesis and its regulation, the molecular and functional pharmacology of CysLT receptors, and an overview of the established and emerging roles of CysLTs in asthma, aspirin-exacerbated respiratory disease, and type 2 inflammation.
半胱氨酰白三烯（CysLTs），即LTC、LTD和LTE，是通过5-脂氧合酶途径从花生四烯酸衍生而来的强效脂质介质。这些介质通过三种不同的G蛋白偶联受体（GPCRs）——CysLT₁、CysLT₂和OXGR1（也称为CysLT₁或GPR99）产生炎症和支气管收缩。虽然CysLT在过敏性炎症和哮喘效应阶段的介导功能已确立一段时间，但最近的研究表明，这些介质及其受体在2型炎症的诱导和放大中具有新的作用。此外，体外研究和小鼠模型已经发现了多种抑制或放大CysLT受体激活和CysLT受体功能的调节机制。本综述概述了CysLT的生物合成及其调节、CysLT受体的分子和功能药理学，以及CysLT在哮喘、阿司匹林加重的呼吸系统疾病和2型炎症中已确立的和新出现的作用。
