ADAP1/CentA1缺失可预防自身免疫性脱髓鞘

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jonathan J. Carver, Wyatt P. Bunner, Rachael R. Denbrock, Changhong Yin, Weihua Huang, Erzsebet M. Szatmari, Alessandro Didonna
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引用次数: 0

摘要

ArfGAP含有双PH结构域蛋白1 (ADAP1),也被称为Centaurin α -1 (CentA1),是一种在中枢神经系统(CNS)中高度表达的肌动蛋白结合蛋白,先前被证明可以调节树突棘的密度和可塑性。在疾病方面,ADAP1/CentA1与阿尔茨海默病(AD)的发病机制、癌症进展和人类免疫缺陷病毒(HIV)的再激活有关。本研究发现,ADAP1/CentA1也参与中枢神经系统自身免疫。我们发现,ADAP1/CentA1缺陷小鼠对实验性自身免疫性脑脊髓炎(EAE)表现出部分抗性,EAE是一种概括多发性硬化症(MS)发病机制的体内疾病模型。多发性硬化症是中枢神经系统的慢性自身免疫性疾病,以局灶性免疫细胞浸润、脱髓鞘和轴突损伤为特征。其病因仍然难以捉摸,但遗传和环境因素有助于疾病风险。通过结合详细的免疫表型分析和单细胞RNA测序(scRNA-seq),我们证明了ADAP1/CentA1是建立EAE起始和进展的充分自身免疫反应所必需的。特别是,目前的研究强调了免疫系统中ADAP1/CentA1的表达主要针对调节性T细胞(Tregs)、单核细胞和自然杀伤细胞(NK)的功能。总之,我们的研究确定了ADAP/CentA1在中枢神经系统外的一种新功能,并有助于阐明外周免疫系统中发生的早期分子事件,以响应致脑性挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination

Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination

Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination

Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination

ArfGAP with dual PH domain-containing protein 1 (ADAP1), also known as Centaurin alpha-1 (CentA1), is an actin-binding protein highly expressed in the central nervous system (CNS) that was previously shown to regulate dendritic spine density and plasticity. In the context of disease, ADAP1/CentA1 has been linked to Alzheimer's disease (AD) pathogenesis, cancer progression, and human immunodeficiency virus (HIV) reactivation. Here, we document that ADAP1/CentA1 is also mechanistically involved in CNS autoimmunity. We show that ADAP1/CentA1 deficient mice exhibit partial resistance to developing experimental autoimmune encephalomyelitis (EAE), an in vivo disease model recapitulating several features of multiple sclerosis (MS) pathogenesis. MS is a chronic autoimmune disorder of the CNS characterized by focal immune cell infiltration, demyelination, and axonal injury. Its etiology is still elusive, but genetic and environmental factors contribute to disease risk. By combining detailed immunophenotyping and single-cell RNA sequencing (scRNA-seq), we demonstrate that ADAP1/CentA1 is necessary for mounting a sufficient autoimmune response for EAE initiation and progression. In particular, the current study highlights that ADAP1/CentA1 expression in the immune system mainly targets the functioning of regulatory T cells (Tregs), monocytes, and natural killer (NK) cells. In summary, our study defines a novel function for ADAP/CentA1 outside of the CNS and helps elucidate the early molecular events taking place in the peripheral immune system in response to encephalitogenic challenges.

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来源期刊
The FASEB Journal
The FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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