Administration of anti-ERMAP antibody ameliorates Alzheimer's disease in mice.
Administration of anti-ERMAP antibody ameliorates Alzheimer's disease in mice.
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DOI：
10.1186/s12974-021-02320-x
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发表时间：
2021-11-13
影响因子：
9.3
通讯作者：
Lai L
中科院分区：
文献类型：
--
作者：
Liu H;Zhao J;Lin Y;Su M;Lai L
阿尔茨海默病（Alzheimer's disease，AD）是一种与年龄相关的神经退行性疾病，以记忆和认知功能的进行性丧失为特征，与β淀粉样蛋白（amyloid-beta，Aβ）斑块相关。免疫细胞在Aβ沉积物的清除中起重要作用。免疫反应由免疫调节剂调节，其中B7家族成员起着至关重要的作用。我们最近鉴定了红细胞膜相关蛋白（ERMAP）作为一种新的B7家族相关的免疫调节剂，并表明ERMAP蛋白影响T细胞和巨噬细胞功能。我们制备了针对ERMAP蛋白的单克隆抗体（mAb），然后确定mAb影响小鼠认知能力和AD病理学的能力。 我们已经证明，抗ERMAP mAb中和了ERMAP的T细胞抑制活性，并在体外增强了巨噬细胞吞噬Aβ的能力。将mAb给予AD小鼠可改善认知能力并降低脑中的Aβ斑块负荷。这与脾脏和脉络丛（CP）中T细胞（尤其是产生IFNγ的T细胞）比例增加、CP中免疫细胞运输分子表达增强以及单核细胞来源的巨噬细胞向脑中迁移增加有关。此外，在抗ERMAP mAb处理的AD小鼠中，血清中抗A β抗体的产生和巨噬细胞对Aβ的吞噬作用增强。我们的研究结果表明，操纵ERMAP通路有可能提供一种新的方法来治疗AD患者。
Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder and characterized by progressive loss of memory and cognitive functions, which are associated with amyloid-beta (Aβ) plaques. Immune cells play an important role in the clearance of Aβ deposits. Immune responses are regulated by immune regulators in which the B7 family members play a crucial role. We have recently identified erythroid membrane-associated protein (ERMAP) as a novel B7 family-related immune regulator and shown that ERMAP protein affects T cell and macrophage functions. We produced a monoclonal antibody (mAb) against ERMAP protein and then determined the ability of the mAb to affect cognitive performance and AD pathology in mice. We have shown that the anti-ERMAP mAb neutralizes the T cell inhibitory activity of ERMAP and enhances macrophages to phagocytose Aβ in vitro. Administration of the mAb into AD mice improves cognitive performance and reduces Aβ plaque load in the brain. This is related to increased proportion of T cells, especially IFNγ-producing T cells, in the spleen and the choroid plexus (CP), enhanced expression of immune cell trafficking molecules in the CP, and increased migration of monocyte-derived macrophages into the brain. Furthermore, the production of anti-Aβ antibodies in the serum and the macrophage phagocytosis of Aβ are enhanced in the anti-ERMAP mAb-treated AD mice. Our results suggest that manipulating the ERMAP pathway has the potential to provide a novel approach to treat AD patients.
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