Bossù Paola, Spalletta Gianfranco, Caltagirone Carlo, Ciaramella Antonio
Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation , Rome , Italy.
Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
Front Immunol. 2015 Dec 16;6:632. doi: 10.3389/fimmu.2015.00632. eCollection 2015.
Alzheimer's diseases (AD) and Parkinson's diseases (PD) are devastating neurodegenerative disturbances, wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs) are key immune orchestrators and players of brain immune surveillance; we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients' blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers, and improve therapeutic approaches for neurodegenerative diseases.
阿尔茨海默病（AD）和帕金森病（PD）是毁灭性的神经退行性疾病，其中神经炎症是一个具有高治疗潜力的慢性致病过程。AD/PD神经免疫过程的主要介质是驻留免疫细胞，但源自外周的免疫细胞也可能参与并在一定程度上改变神经炎症。具体而言，血源性髓样细胞成为AD/PD进展和易感性的关键组成部分。其中，树突状细胞（DCs）是大脑免疫监视的关键免疫协调者和参与者；我们将它们视为AD和PD的潜在介质以及用于阐明髓样细胞在神经退行性变中作用的相关细胞模型。因此，我们总结并讨论了新出现的数据，这些数据表明血源性DCs在实验性和人类神经退行性疾病中发挥作用。特别是在人类中，DCs通过与神经退行性变相关的致病因素进行体外培养而发生改变，并且在AD患者中失调，而AD和PD患者血液中DC前体的水平降低，这可能是它们被招募到大脑的一个指标。总体而言，我们强调需要探索DCs对神经退行性变的影响，以揭示具有致病重要性的外周免疫机制，识别潜在的生物标志物，并改善神经退行性疾病的治疗方法。
