Thome Aaron D, Atassi Farah, Wang Jinghong, Faridar Alireza, Zhao Weihua, Thonhoff Jason R, Beers David R, Lai Eugene C, Appel Stanley H
Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.
NPJ Parkinsons Dis. 2021 May 13;7(1):41. doi: 10.1038/s41531-021-00188-5.
Inflammation is a pathological hallmark of Parkinson's disease (PD). Chronic pro-inflammatory responses contribute to the loss of neurons in the neurodegenerative process. The present study was undertaken to define the peripheral innate and adaptive immune contributions to inflammation in patients with PD. Immunophenotyping revealed a shift of peripheral myeloid and lymphoid cells towards a pro-inflammatory phenotype. Regulatory T cells (Tregs) were reduced in number, and their suppression of T responder proliferation decreased. The PD Tregs did not suppress activated pro-inflammatory myeloid cells. Ex vivo expansion of Tregs from patients with PD restored and enhanced their suppressive functions while expanded Tregs displayed increased expression of foxp3, il2ra (CD25), nt5e (CD73), il10, il13, ctla4, pdcd1 (PD1), and gzmb. Collectively, these findings documented a shift towards a pro-inflammatory peripheral immune response in patients with PD; the loss of Treg suppressive functions may contribute significantly to this response, supporting PD as a disorder with extensive systemic pro-inflammatory responses. The restoration and enhancement of Treg suppressive functions following ex vivo expansion may provide a potential cell therapeutic approach for patients with PD.
炎症是帕金森病（PD）的一个病理特征。慢性促炎反应在神经退行性变过程中导致神经元丢失。本研究旨在确定外周固有免疫和适应性免疫对PD患者炎症的影响。免疫表型分析显示外周髓样细胞和淋巴细胞向促炎表型转变。调节性T细胞（Tregs）数量减少，其对T应答细胞增殖的抑制作用降低。PD患者的Tregs不能抑制活化的促炎髓样细胞。体外扩增PD患者的Tregs可恢复并增强其抑制功能，同时扩增后的Tregs显示foxp3、il2ra（CD25）、nt5e（CD73）、il10、il13、ctla4、pdcd1（PD1）和gzmb的表达增加。总的来说，这些发现证明PD患者外周免疫反应向促炎方向转变；Tregs抑制功能的丧失可能对此反应有显著贡献，支持PD是一种具有广泛全身促炎反应的疾病。体外扩增后Tregs抑制功能的恢复和增强可能为PD患者提供一种潜在的细胞治疗方法。
