小胶质细胞在中枢神经系统和胶质瘤中的免疫学作用及其相关研究进展

血脑屏障在正常情况下能够保证脑的内环境的高度稳定性,以利于中枢神经系统的机能活动。中枢神经系统内缺乏各种常见的抗原递呈细胞,但小胶质细胞可作为潜在的抗原递呈细胞将MHC分子结合的抗原肽与T细胞受体结合介导相应的免疫反应。而在胶质瘤组织中高度浸润的小胶质细胞可通过对肿瘤微环境的免疫抑制而促进肿瘤生长。一旦小胶质细胞被激活就能成为强大的免疫效应细胞,在中枢神经系统损伤和疾病中发挥多种生物学功能。     

小胶质细胞在创伤性脑损伤中作用的研究进展

小胶质细胞(MG)是人体中枢神经系统(CNS)固有的免疫细胞成分,正常情况下处于静止状态,缺乏吞噬功能,仅具有一定的迁移能力和吞饮功能。但作为CNS的第一道防线,可在CNS病变时被激活发挥类似于巨噬细胞的吞噬保护功能;当功能发生紊乱时又会加重病变的发生发展,从而具有修复和损伤的"双刃剑"作用。创伤性脑损伤(TBI)是一个影响社会的重大健康和社会经济问题,包括突然加速或减速的间接损伤、冲击或撞击引起的脑挫伤和爆炸伤等。TBI发生时会激活MG,使其增生与聚集,同时常伴有免疫表型、细胞形态与功能等一系列的变化。本文旨在针对MG参与TBI病理生理过程进行综述。     

小胶质细胞引起和促进阿尔茨海默病的研究进展

小胶质细胞是神经系统免疫细胞,具有双重特性,既可以通过免疫反应增强吞噬能力、释放抗炎因子维持脑组织的稳态和保护神经元,又可以增加炎性反应、降低有害蛋白清除能力损伤神经元.受衰老的影响,在基因表达方面,小胶质细胞CD33表达增加而髓系细胞触发受体2(TREM2)表达减少;在活化表型方面,衰老环境下的小胶质细胞更倾向活化为...     

小胶质细胞及其相关炎性信号通路

小胶质细胞作为中枢系统重要的免疫效应细胞,在中枢神经系统损伤及疾病处理中发挥着不可忽视的作用。本文从小胶质细胞的生物学特性及其相关的炎性信号通路（Notch信号通路、Toll样信号通路、AMPK信号通路、NF-κB信号通路）两大方面探讨,以期为临床抗炎药物的开发提供新思路。     

小胶质细胞在中枢神经系统介导的免疫损伤与保护作用的研究进展

20世纪初,人们对小胶质细胞进行了较为详细的观察,由此开始了对这一重要免疫细胞的深入研究。小胶质细胞作为中枢神经系统(CNS)的一种组织巨噬细胞,在成熟大脑稳定状态、组织发生过程以及损伤、疾病、修复等病理状态具有不同的形态和功能,并具有不同的免疫活性。其在CNS的功能和疾病介导作用,是深入研究的热点。     

小胶质细胞在神经系统病变中的作用

小胶质细胞(micro-glia,MG)是广泛分布于哺乳动物中枢神经系统的一种具有运动活性的细胞[1]。1891年Nissl首次描述MG后,MG一直以来都很受人们的重视。1919年,西班牙学者Del Rion-Horte-ga用碳酸银染色法将MG与其它细胞区分开来,并证明它是中枢神经系统最具代表性的免疫细胞。在     

小胶质细胞在自杀中的作用及其机制

自杀的发生率日益提高,但是其发生机制尚不清楚。近年来的研究表明神经生物学因素与自杀有着密切的关系。作为中枢神经系统的重要组成部分,小胶质细胞对神经递质代谢、免疫调节和神经炎症等都有较大影响,过度激活的小胶质细胞被认为在自杀中发挥了重要作用。本文将对小胶质细胞状态与自杀的关系,以及小胶质细胞介导的神经炎症、神经免疫、应激反应过程影响自杀行为的相关机制进行综述,以期为自杀的神经机制研究提供思路,为自杀预防策略的制定提供理论依据。     

小胶质细胞与脑缺血

自从1891年Nissl首次描述小胶质细胞以来,它一直受到人们的重视,学术争论不断,现在人们注意到小胶质细胞作为中枢神经系统固有的免疫效应细胞参与其免疫反应和病理过程。研究发现小胶质细胞在脑缺血后异常活跃,脑缺血所激发的小胶质细胞反应极为复杂,现将小胶质细胞在脑缺血病理过程中形态变化和保护作用等作一综述。     

星形胶质细胞在中枢神经系统炎性疾病中作用的研究进展

星形胶质细胞应对多种中枢神经系统(CNS)损伤并活化为反应性星形胶质细胞,通过神经保护或神经毒性作用影响CNS的组织修复和神经炎性疾病的发生和发展.反应性星形胶质细胞的发生机制主要与其表型转化及下游炎性通路的激活相关.探索反应性星形胶质细胞的特征及其对CNS炎性疾病的调控机制可能为CNS炎性疾病的发病机制提供新见解和潜在干预靶点.     

Role of microglia in central nervous system infections

The nature of microglia fascinated many prominent researchers in the 19th and early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega formulated a number of concepts regarding the function of these resident macrophages of the brain parenchyma that remain relevant to this day. However, a renaissance of interest in microglia occurred toward the end of the 20th century, fueled by the recognition of their role in neuropathogenesis of infectious agents, such as human immunodeficiency virus type 1, and by what appears to be their participation in other neurodegenerative and neuroinflammatory disorders. During the same period, insights into the physiological and pathological properties of microglia were gained from in vivo and in vitro studies of neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed in this article. New concepts that have emerged from these studies include the importance of cytokines and chemokines produced by activated microglia in neurodegenerative and neuroprotective processes and the elegant but astonishingly complex interactions between microglia, astrocytes, lymphocytes, and neurons that underlie these processes. It is proposed that an enhanced understanding of microglia will yield improved therapies of central nervous system infections, since such therapies are, by and large, sorely needed.     

Copolymer effects on microglia and T cells in the central nervous system of humanized mice

The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85-99-specific T cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85-99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85-99 and activate transgenic T cells. In vitro microglia up-regulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-gamma, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85-99-induced EAE. Interestingly, microglia expressed the full-length gammabeta and alphabeta subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85-99 was composed of equal numbers of hVbeta2+ MPB85-99-specific transgenic and hVbeta2- endogenous T cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hVbeta2- endogenous T cells.     

Immune regulatory effects of central nervous system antigens in culture

Evidence from several different experimental systems suggests that regulatory cells specific for self-antigens exist in the normal immune repertoire, and that these cells are necessary for maintenance of self-tolerance and prevention of autoimmune disease. We attempted to demonstrate the existence of regulatory cells specific for central nervous system (CNS) antigens in normal mice. We tested the effects of myelin basic protein (MBP), glial fibrillary acidic protein (GFAP) and a mixture of soluble brain proteins (SBP) on cultured splenocytes. MBP at 50 microg/ml inhibited antigen-driven proliferation and this suppressive effect could be partially blocked by neutralizing antibodies to transforming growth factor (TGF)-beta. MBP decreased expression of mRNA for the cytokines IL-2 and IFN-gamma, and slightly increased mRNA expression for TGF-beta. These effects did not appear to be mediated by regulatory cells specific for MBP, since MBP also suppressed proliferation in MBP-deficient shiverer mice and the suppressive effect could not be reproduced with selected MBP peptides. SBP at 250 microg/ml also inhibited antigen-driven proliferation, but this effect could not be blocked by neutralizing antibodies against IL-4, IL-10 or TGF-beta. SBP reduced expression of mRNA for IL-2, IL-10 and TGF-beta. These results are more consistent with the presence of a soluble inhibitory factor than with the action of SBP-specific regulatory cells. GFAP had no significant effect on proliferation. These results do not support the existence of regulatory cells specific for CNS antigens. Further investigation into non-antigen-specific mechanisms will be important in defining how autoimmune damage in the CNS is prevented.     

小胶质细胞对坐骨神经损伤后的反应

目的 探讨对小细胞对周围神经损伤的反应。方法 用Thymosin β4抗体标汜小胶质细胞,在大鼠坐骨神经切断后1、2、3、4、6、8、10、12、14、18、20d,检测其脊髓及脑干内小胶质细胞、并对有变化者用电镜观察。结果 发现在坐骨神经损伤后第1天开始至第20天,在相应脊髓节段同侧灰质及脑干的薄束核内见到许多体积增大、数量增多的Thymosin β4标记阳性细胞即激活的小胶质细胞。激活的小胶质细胞数量在损伤后第3天达到高峰,然后逐渐下降,至第20天后才消失;与相应脊髓节段相比较,薄束核内激活的小胶质细胞数量要少些。电镜观察发现,这些激活的小胶质细胞多位于神经元胞体的周围并与神经元有密切的接触。结论 周围神经损伤,可引起相应中枢部位的小胶质细胞激活与增殖．其作用可能与保护受损的神经元、维护神经元的周围环境有关。     

NG2与中枢神经系统疾病研究新进展

<正>NG2是一种硫酸软骨素蛋白多糖(chondroitin sulphate peoteoglycan,CSPG),在发育及成熟哺乳动物中枢神经系统中广泛表达。表达NG2的细胞根据其密度、分布、独特的细胞标记和生理性能归为一类独特的神经胶质细胞。NG2细胞具有神经干细胞的部分特性和分化产生不同细胞系的潜     

The microbiota–microglia axis in central nervous system disorders

The innate immune system in the central nervous system (CNS) is mainly represented by specialized tissue‐resident macrophages, called microglia. In the past years, various species‐, host‐ and tissue‐specific as well as environmental factors were recognized that essentially affect microglial properties and functions in the healthy and diseased brain. Host microbiota are mostly residing in the gut and contribute to microglial activation states, for example, via short‐chain fatty acids (SCFAs) or aryl hydrocarbon receptor (AhR) ligands. Thereby, the gut microorganisms are deemed to influence numerous CNS diseases mediated by microglia. In this review, we summarize recent findings of the interaction between the host microbiota and the CNS in health and disease, where we specifically highlight the resident gut microbiota as a crucial environmental factor for microglial function as what we coin “the microbiota‐microglia axis.”     

Cannabinoid receptors in microglia of the central nervous system: immune functional relevance

Microglia, resident macrophages of the brain, function as immune effector and accessory cells. Paradoxically, they not only play a role in host defense and tissue repair but also have been implicated in a variety of neuropathological processes. Microglia, in addition to exhibiting phenotypic markers for macrophages, express CB1 and CB2 cannabinoid receptors. Recent studies suggest the existence of a third, yet-to-be cloned, non-CB1, non-CB2 cannabinoid receptor. These receptors appear to be functionally relevant within defined windows of microglial activation state and have been implicated as linked to cannabinoid modulation of chemokine and cytokine expression. The recognition that microglia express cannabinoid receptors and that their activation results in modulation of select cellular activities suggests that they may be amenable to therapeutic manipulation for ablating untoward inflammatory responses in the central nervous system.     

Oligodendrocyte‐microglia cross‐talk in the central nervous system

Communication between the immune system and the central nervous system (CNS) is exemplified by cross‐talk between glia and neurons shown to be essential for maintaining homeostasis. While microglia are actively modulated by neurons in the healthy brain, little is known about the cross‐talk between oligodendrocytes and microglia. Oligodendrocytes, the myelin‐forming cells in the CNS, are essential for the propagation of action potentials along axons, and additionally serve to support neurons by producing neurotrophic factors. In demyelinating diseases such as multiple sclerosis, oligodendrocytes are thought to be the victims. Here, we review evidence that oligodendrocytes also have strong immune functions, express a wide variety of innate immune receptors, and produce and respond to chemokines and cytokines that modulate immune responses in the CNS. We also review evidence that during stress events in the brain, oligodendrocytes can trigger a cascade of protective and regenerative responses, in addition to responses that elicit progressive neurodegeneration. Knowledge of the cross‐talk between microglia and oligodendrocytes may continue to uncover novel pathways of immune regulation in the brain that could be further exploited to control neuroinflammation and degeneration.