T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases.
T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases.
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DOI：
10.1186/s12974-014-0201-8
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发表时间：
2014-12-02
影响因子：
9.3
通讯作者：
Pacheco R
中科院分区：
文献类型：
--
作者：
González H;Pacheco R
神经炎症涉及几种神经退行性疾病，并且新出现的证据表明它构成了神经退行性疾病进展所需的关键过程。小胶质细胞活化构成神经炎症的中心事件。此外，小胶质细胞不仅可以被激活具有炎症和神经毒性表型（M1样表型），而且它们还可以获得以产生抗炎介质和神经营养因子为特征的神经支持功能表型（M2样表型）。重要的是，在过去的十年中，一些研究表明，CD 4 + T细胞浸润中枢神经系统（CNS）在许多神经退行性疾病，其中它们的参与对小胶质细胞活化和随之而来的神经退行性疾病的结果有着至关重要的影响。在这篇综述中，我们重点分析了不同亚群的CD 4 + T细胞浸润中枢神经系统的相互作用，以及它们如何参与调节神经炎症和神经变性的结果在帕金森病，阿尔茨海默病，肌萎缩侧索硬化症和多发性硬化症的背景下。在这方面，致脑炎性炎性CD 4 + T细胞，如Th 1、Th 17、GM-CSF生产者CD 4 + T细胞和γδ T细胞，强烈地促进慢性神经炎症，从而使神经变性过程永久化。相反，致脑炎性或脑膜T细胞和Th 2细胞减少小胶质细胞中的炎症功能，并促进神经支持性微环境。此外，尽管一些神经退行性疾病如多发性硬化症、帕金森病和阿尔茨海默病涉及炎性CD 4 + T细胞“自然地”参与，但其他神经退行性疾病如肌萎缩性侧索硬化症的生理病理学与延迟神经退行性过程的抗炎性CD 4 + T细胞的参与相关。因此，目前的证据支持这样的假设，即参与的CD 4 + T细胞对中枢神经系统抗原构成了一个关键组成部分，在调节神经退行性过程的进展。
Neuroinflammation is involved in several neurodegenerative disorders and emerging evidence indicates that it constitutes a critical process that is required for the progression of neurodegeneration. Microglial activation constitutes a central event in neuroinflammation. Furthermore, microglia can not only be activated with an inflammatory and neurotoxic phenotype (M1-like phenotype), but they also can acquire a neurosupportive functional phenotype (M2-like phenotype) characterised by the production of anti-inflammatory mediators and neurotrophic factors. Importantly, during the past decade, several studies have shown that CD4+ T-cells infiltrate the central nervous system (CNS) in many neurodegenerative disorders, in which their participation has a critical influence on the outcome of microglial activation and consequent neurodegeneration. In this review, we focus on the analysis of the interplay of the different sub-populations of CD4+ T-cells infiltrating the CNS and how they participate in regulating the outcome of neuroinflammation and neurodegeneration in the context of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis. In this regard, encephalitogenic inflammatory CD4+ T-cells, such as Th1, Th17, GM-CSF-producer CD4+ T-cells and γδT-cells, strongly contribute to chronic neuroinflammation, thus perpetuating neurodegenerative processes. In contrast, encephalitogenic or meningeal Tregs and Th2 cells decrease inflammatory functions in microglial cells and promote a neurosupportive microenvironment. Moreover, whereas some neurodegenerative disorders such as multiple sclerosis, Parkinson’s disease and Alzheimer’s disease involve the participation of inflammatory CD4+ T-cells 'naturally', the physiopathology of other neurodegenerative diseases, such as amyotrophic lateral sclerosis, is associated with the participation of anti-inflammatory CD4+ T-cells that delay the neurodegenerative process. Thus, current evidence supports the hypothesis that the involvement of CD4+ T-cells against CNS antigens constitutes a key component in regulating the progression of the neurodegenerative process.
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DOI：
10.1016/j.bbadis.2010.07.008
发表时间：
2011-02
影响因子：
6.2
作者：
Chastain, Emily M. L.;Duncan, D'Anne S.;Rodgers, Jane M.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
DOI：
10.1093/brain/awr074
发表时间：
2011-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Beers DR;Henkel JS;Zhao W;Wang J;Huang A;Wen S;Liao B;Appel SH
通讯作者：
Appel SH
影响因子：
15.9
作者：
Brochard, Vanessa;Combadiere, Behazine;Hunot, Stephane
通讯作者：
Hunot, Stephane
影响因子：
6.1
作者：
Cintia Ferrari, Carina;Pott Godoy, Maria Clara;Juan Pitossi, Fernando
通讯作者：
Juan Pitossi, Fernando