Liang Fengchu, Xu Zongtang, Ding Liuyan, Zhu Ziting, Chen Minshan, Shu Hui, Huang Xingting, Su Zhongqiang, Wang Xiaobei, Xiao Yousheng, Huang Shuxuan, Mai Dongmei, Yi Erkang, Xu Pingyi, Zhang Wenlong
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
J Hazard Mater. 2025 Aug 15;494:138569. doi: 10.1016/j.jhazmat.2025.138569. Epub 2025 May 13.
Biomass fuel (BMF) exposure is known to cause respiratory inflammation, but its impact on the central nervous system (CNS) and the mechanisms underlying this effect remain unclear. BMF combustion releases particulate matter (PM2.5), triggering systemic inflammation, which is linked to an increased risk of neurodegenerative diseases such as Parkinson's disease (PD). This study revealed that prolonged BMF exposure leads to dopaminergic neuron loss, increased α-synuclein (α-syn) phosphorylation, and neuroinflammation, resulting in motor and cognitive impairments in mice. Mechanistically, BMF activates the interleukin-17A (IL-17A) signalling pathway in the periphery, promoting Th cell infiltration across the bloodbrain barrier, which stimulates astrocytes to release IL-17A and activates IL-17 receptor A (IL-17RA) on microglia. Transcriptomic and metabolomic analyses revealed that BMF exposure significantly disrupts immune and neurotransmitter pathways. Importantly, IL-17A knockout (IL-17A) mice exhibit marked improvements in motor and cognitive functions and reduced neuroinflammation following BMF exposure. These findings identify IL-17A as a critical mediator of the lungbrain axis, orchestrating PD-related immune responses within both the CNS and peripheral nervous system. The IL-17A pathway represents a promising therapeutic target for PD and the related neuroinflammatory changes associated with environmental pollutant exposure.
已知生物质燃料（BMF）暴露会导致呼吸道炎症，但其对中枢神经系统（CNS）的影响以及这种影响的潜在机制仍不清楚。BMF燃烧会释放颗粒物（PM2.5），引发全身炎症，这与帕金森病（PD）等神经退行性疾病风险增加有关。本研究表明，长期暴露于BMF会导致多巴胺能神经元丢失、α-突触核蛋白（α-syn）磷酸化增加和神经炎症，从而导致小鼠出现运动和认知障碍。从机制上讲，BMF在外周激活白细胞介素-17A（IL-17A）信号通路，促进Th细胞穿过血脑屏障浸润，刺激星形胶质细胞释放IL-17A并激活小胶质细胞上的IL-17受体A（IL-17RA）。转录组学和代谢组学分析表明，BMF暴露会显著破坏免疫和神经递质通路。重要的是，IL-17A基因敲除（IL-17A -/-）小鼠在暴露于BMF后运动和认知功能有显著改善，神经炎症减轻。这些发现确定IL-17A是肺-脑轴的关键介质，协调中枢神经系统和外周神经系统内与PD相关的免疫反应。IL-17A通路是治疗PD以及与环境污染物暴露相关的神经炎症变化的一个有前景的治疗靶点。
