美国哈佛医学院Filip K. Swirski、Rudolph E. Tanzi等研究人员合作发现，星形细胞的白细胞介素-3对小胶质细胞进行编程并限制阿尔茨海默病的发生。相关论文于2021年7月14日在线发表在《自然》杂志上。

研究人员表示，胶质细胞生态系统内的交流对神经元和大脑健康至关重要。胶质细胞对阿尔茨海默病（AD）患者大脑中β-淀粉样蛋白（Aβ）和神经纤维性tau的积累和清除的影响知之甚少，尽管人们越来越意识到这些相互作用是具有治疗意义的。

在人类和小鼠中，研究人员发现，星形胶质细胞来源的白细胞介素-3（IL-3）能使小胶质细胞改善AD的病理状况。在识别Aβ沉积后，小胶质细胞增加了IL-3Rα的表达，这是IL-3的特异性受体（也被称为CD123），从而使它们对IL-3有反应。星形胶质细胞组成性地产生IL-3，这会引起小胶质细胞的转录、形态和功能编程，进而赋予它们急性免疫反应程序，增强的运动能力，以及聚集和清除Aβ和tau聚集物的能力。这些变化限制了AD病理学和认知能力的下降。这些研究结果确定IL-3是星形胶质细胞-小胶质细胞交流对话的一个关键媒介，也是AD治疗干预的一个节点。

附：英文原文

Title: Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease

Author: Cameron S. McAlpine, Joseph Park, Ana Griciuc, Eunhee Kim, Se Hoon Choi, Yoshiko Iwamoto, Mt G. Kiss, Kathleen A. Christie, Claudio Vinegoni, Wolfram C. Poller, John E. Mindur, Christopher T. Chan, Shun He, Henrike Janssen, Lai Ping Wong, Jeffrey Downey, Sumnima Singh, Atsushi Anzai, Florian Kahles, Mehdi Jorfi, Paolo Fumene Feruglio, Ruslan I. Sadreyev, Ralph Weissleder, Benjamin P. Kleinstiver, Matthias Nahrendorf, Rudolph E. Tanzi, Filip K. Swirski

Issue&Volume: 2021-07-14

Abstract: Communication within the glial cell ecosystem is essential for neuronal and brain health1,2,3. The influence of glial cells on the accumulation and clearance of β-amyloid (Aβ) and neurofibrillary tau in the brains of individuals with Alzheimer’s disease (AD) is poorly understood, despite growing awareness that these are therapeutically important interactions4,5. Here we show, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs microglia to ameliorate the pathology of AD. Upon recognition of Aβ deposits, microglia increase their expression of IL-3Rα—the specific receptor for IL-3 (also known as CD123)—making them responsive to IL-3. Astrocytes constitutively produce IL-3, which elicits transcriptional, morphological, and functional programming of microglia to endow them with an acute immune response program, enhanced motility, and the capacity to cluster and clear aggregates of Aβ and tau. These changes restrict AD pathology and cognitive decline. Our findings identify IL-3 as a key mediator of astrocyte–microglia cross-talk and a node for therapeutic intervention in AD.

DOI: 10.1038/s41586-021-03734-6

Source: https://www.nature.com/articles/s41586-021-03734-6