Satyanarayanan Senthil Kumaran, Han Zixu, Xiao Jingwei, Yuan Qiuju, Yung Wing Ho, Ke Ya, Chang Raymond Chuen-Chung, Zhu Maria Huachen, Su Huanxing, Su Kuan-Pin, Qin Dajiang, Lee Suki Man Yan
Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Hong Kong, China.
Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Hong Kong, China; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510799, China; School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Brain Behav Immun. 2025 Jan;123:483-499. doi: 10.1016/j.bbi.2024.10.007. Epub 2024 Oct 6.
Neurodegenerative diseases (NDs) demonstrate a complex interaction with the immune system, challenging the traditional view of the brain as an "immune-privileged" organ. Microglia were once considered the sole guardians of the brain's immune response. However, recent research has revealed the critical role of peripheral immune cells located in key brain regions like the meninges, choroid plexus, and perivascular spaces. These previously overlooked cells are now recognized as contributors to the development and progression of NDs. This newfound understanding opens doors for pioneering therapeutic strategies. By targeting these peripheral immune cells, we may be able to modulate the brain's immune environment, offering an alternative approach to treat NDs and circumvent the challenges posed by the blood-brain barrier. This comprehensive review will scrutinize the latest findings on the complex interactions between these peripheral immune cells and NDs. It will also critically assess the prospects of targeting these cells as a ground-breaking therapeutic avenue for these debilitating disorders.
神经退行性疾病（NDs）与免疫系统表现出复杂的相互作用，挑战了大脑是“免疫豁免”器官的传统观念。小胶质细胞曾被认为是大脑免疫反应的唯一守护者。然而，最近的研究揭示了位于脑膜、脉络丛和血管周围间隙等关键脑区的外周免疫细胞的关键作用。这些先前被忽视的细胞现在被认为是神经退行性疾病发生和发展的促成因素。这一新发现为开创性的治疗策略打开了大门。通过靶向这些外周免疫细胞，我们或许能够调节大脑的免疫环境，提供一种治疗神经退行性疾病的替代方法，并规避血脑屏障带来的挑战。这篇综述将仔细研究这些外周免疫细胞与神经退行性疾病之间复杂相互作用的最新发现。它还将批判性地评估将这些细胞作为治疗这些使人衰弱疾病的开创性治疗途径的前景。
