Alpha synuclein, the culprit in Parkinson disease, is required for normal immune function.
Alpha synuclein, the culprit in Parkinson disease, is required for normal immune function.
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DOI：
10.1016/j.celrep.2021.110090
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发表时间：
2022-01-11
期刊：
影响因子：
8.8
通讯作者：
Oppenheim, Joost J.
中科院分区：
文献类型：
--
作者：
Alam, Md Masud;Yang, De;Li, Xiao-Qing;Liu, Jia;Back, Timothy Carrel;Trivett, Anna;Karim, Baktiar;Barbut, Denise;Zasloff, Michael;Oppenheim, Joost J.
α-突触核蛋白（αS）与帕金森病（PD）的发生发展有因果关系;然而，其在正常脊椎动物生理学中的作用仍不清楚。最近的研究表明，αS是由诺如病毒感染诱导的儿童肠神经系统，并保护小鼠免受致命的嗜神经病毒感染。此外，αS是一种有效的吞噬细胞趋化激活剂。在这份报告中，使用野生型和αS基因敲除小鼠，我们表明αS是炎症和免疫反应的关键介质。αS是对引入腹腔的细菌肽聚糖产生正常炎症反应以及腹膜内免疫后抗原特异性和T细胞反应所必需的。此外，我们表明，神经细胞是免疫能力所需的αS的来源。我们的报告支持αS在PD个体的神经系统内蓄积是由于炎症/免疫反应的假设。Alam等人表明，胃肠系统神经元产生的αS对于腹膜炎症和全身抗原特异性免疫应答的表现至关重要，这反过来可能促进神经元αS蓄积并有助于帕金森病的发生和/或进展。
Alpha-synuclein (αS) is causally involved in the development of Parkinson disease (PD); however, its role in normal vertebrate physiology has remained unknown. Recent studies demonstrate that αS is induced by noroviral infection in the enteric nervous system of children and protects mice against lethal neurotropic viral infection. Additionally, αS is a potent chemotactic activator of phagocytes. In this report, using both wild-type and αS knockout mice, we show that αS is a critical mediator of inflammatory and immune responses. αS is required for the development of a normal inflammatory response to bacterial peptidoglycan introduced into the peritoneal cavity as well as antigen-specific and T cell responses following intraperitoneal immunization. Furthermore, we show that neural cells are the sources of αS required for immune competence. Our report supports the hypothesis that αS accumulates within the nervous system of PD individuals because of an inflammatory/immune response. Alam et al. show that αS produced by the neurons of the gastrointestinal system is critical for the manifestation of peritoneal inflammation and systemic antigen-specific immune responses, which may in turn, promote neuronal αS accumulation and contribute to the development and/or progression of Parkinson disease.
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影响因子：
4.7
作者：
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通讯作者：
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168.9
作者：
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来自淋巴结T细胞区域的树突状细胞上的主要组织相容性复合物II并肽复合物。
DOI：
10.1084/jem.186.5.665
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Inaba K;Pack M;Inaba M;Sakuta H;Isdell F;Steinman RM
通讯作者：
Steinman RM