Ma Qimin, Wang Yusong, Zhu Feng
Department of Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
These authors contributed equally to this work.
Eur Respir Rev. 2025 Sep 17;34(177). doi: 10.1183/16000617.0086-2025. Print 2025 Jul.
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by dysregulated inflammation, immune imbalance and impaired alveolar repair. Despite advances in supportive care, effective targeted therapies remain limited. Palmitoylation, a reversible lipid-based post-translational modification, has recently emerged as a regulatory mechanism in ARDS pathogenesis. Acting in a context-dependent manner, palmitoylation affects key processes, including immune activation, programmed cell death and epithelial remodelling. Accumulating evidence suggests that palmitoylation may exert dual roles in ARDS: it can promote inflammation and immune evasion in the early phase, while contributing to resolution and tissue repair during later stages. This review summarises current findings regarding the spatial and temporal regulation of palmitoylation in immune and structural cells involved in ARDS, including its effects on inflammasome activation, epithelial-immune interactions and fibrotic progression. Therapeutic approaches under investigation include selective inhibition of palmitoyltransferases (zinc finger aspartate-histidine-histidine-cysteine motif-containing-type palmitoyltransferase family), modulation of depalmitoylation enzymes and substrate-targeted strategies. Several preclinical studies support the feasibility of targeting palmitoylation to reduce lung injury and improve immune regulation. Overall, palmitoylation represents a potential regulatory node in ARDS pathophysiology. Further research is required to clarify its cell-specific functions and to assess the translational potential of palmitoylation-based interventions.
急性呼吸窘迫综合征（ARDS）是一种危及生命的疾病，其特征为炎症调节异常、免疫失衡和肺泡修复受损。尽管支持治疗取得了进展，但有效的靶向治疗仍然有限。棕榈酰化是一种可逆的基于脂质的翻译后修饰，最近已成为ARDS发病机制中的一种调节机制。棕榈酰化以依赖于上下文的方式发挥作用，影响关键过程，包括免疫激活、程序性细胞死亡和上皮重塑。越来越多的证据表明，棕榈酰化在ARDS中可能发挥双重作用：它可以在早期促进炎症和免疫逃逸，而在后期有助于炎症消退和组织修复。本综述总结了目前关于ARDS相关免疫细胞和结构细胞中棕榈酰化的空间和时间调节的研究结果，包括其对炎性小体激活、上皮-免疫相互作用和纤维化进展的影响。正在研究的治疗方法包括选择性抑制棕榈酰转移酶（含锌指天冬氨酸-组氨酸-组氨酸-半胱氨酸基序型棕榈酰转移酶家族）、调节去棕榈酰化酶和底物靶向策略。多项临床前研究支持靶向棕榈酰化以减轻肺损伤和改善免疫调节的可行性。总体而言，棕榈酰化是ARDS病理生理学中一个潜在的调节节点。需要进一步研究以阐明其细胞特异性功能，并评估基于棕榈酰化的干预措施的转化潜力。
