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Depletion of NK Cells Improves Cognitive Function in the Alzheimer Disease Mouse Model
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-05 , DOI: 10.4049/jimmunol.2000037
Yuanyue Zhang 1 , Ivan Ting Hin Fung 1 , Poornima Sankar 1 , Xiangyu Chen 1 , Lisa S Robison 2 , Longyun Ye 1 , Shanti S D'Souza 1 , Abigail E Salinero 2 , Marcy L Kuentzel 3 , Sridar V Chittur 3 , Wenzheng Zhang 4 , Kristen L Zuloaga 5 , Qi Yang 6
Affiliation  

Key Points NK cells exhibit enhanced proinflammatory phenotype in 3xTg-AD mice. Depletion of NK cells enhances cognitive function of 3xTg-AD mice. Depletion of NK cells alleviates neuroinflammation in 3xTg-AD mice. Despite mounting evidence suggesting the involvement of the immune system in regulating brain function, the specific role of immune and inflammatory cells in neurodegenerative diseases remain poorly understood. In this study, we report that depletion of NK cells, a type of innate lymphocytes, alleviates neuroinflammation, stimulates neurogenesis, and improves cognitive function in a triple-transgenic Alzheimer disease (AD) mouse model. NK cells in the brains of triple-transgenic AD mouse model (3xTg-AD) mice exhibited an enhanced proinflammatory profile. Depletion of NK cells by anti-NK1.1 Abs drastically improved cognitive function of 3xTg-AD mice. NK cell depletion did not affect amyloid β concentrations but enhanced neurogenesis and reduced neuroinflammation. Notably, in 3xTg-AD mice depleted of NK cells, microglia demonstrated a homeostatic-like morphology, decreased proliferative response and reduced expression of neurodestructive proinflammatory cytokines. Together, our results suggest a proinflammatory role for NK cells in 3xTg-AD mice and indicate that targeting NK cells might unlock novel strategies to combat AD.

中文翻译:

耗尽 NK 细胞可改善阿尔茨海默病小鼠模型的认知功能

关键点 NK 细胞在 3xTg-AD 小鼠中表现出增强的促炎表型。NK 细胞的消耗增强了 3xTg-AD 小鼠的认知功能。耗尽 NK 细胞可减轻 3xTg-AD 小鼠的神经炎症。尽管越来越多的证据表明免疫系统参与调节大脑功能,但免疫和炎症细胞在神经退行性疾病中的具体作用仍然知之甚少。在这项研究中,我们报告了在三重转基因阿尔茨海默病 (AD) 小鼠模型中消耗 NK 细胞(一种先天淋巴细胞)可减轻神经炎症、刺激神经发生并改善认知功能。三重转基因 AD 小鼠模型 (3xTg-AD) 小鼠大脑中的 NK 细胞表现出增强的促炎特征。通过抗 NK1 消耗 NK 细胞。1 Abs 显着改善了 3xTg-AD 小鼠的认知功能。NK 细胞耗竭不影响淀粉样蛋白 β 浓度,但会增强神经发生并减少神经炎症。值得注意的是,在耗尽 NK 细胞的 3xTg-AD 小鼠中,小胶质细胞表现出类似稳态的形态,减少增殖反应并减少神经破坏性促炎细胞因子的表达。总之,我们的结果表明 NK 细胞在 3xTg-AD 小鼠中具有促炎作用,并表明靶向 NK 细胞可能会开启对抗 AD 的新策略。减少增殖反应和减少神经破坏性促炎细胞因子的表达。总之,我们的结果表明 NK 细胞在 3xTg-AD 小鼠中具有促炎作用,并表明靶向 NK 细胞可能会开启对抗 AD 的新策略。减少增殖反应和减少神经破坏性促炎细胞因子的表达。总之,我们的结果表明 NK 细胞在 3xTg-AD 小鼠中具有促炎作用,并表明靶向 NK 细胞可能会开启对抗 AD 的新策略。
更新日期:2020-06-05
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