The role of microglia in central nervous system immunity and glioma immunology.
The role of microglia in central nervous system immunity and glioma immunology.
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DOI：
10.1016/j.jocn.2009.05.006
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发表时间：
2010-01
影响因子：
2
通讯作者：
Parsa, Andrew T.
中科院分区：
文献类型：
--
作者：
Yang, Isaac;Han, Seunggu J.;Kaur, Gurvinder;Crane, Courtney;Parsa, Andrew T.
关键词：
中枢神经系统（CNS）历来被认为是一种免疫特权器官，缺乏淋巴系统，并通过血脑屏障屏蔽循环系统。小胶质细胞是中枢神经系统细胞群中一个丰富的部分，占总胶质细胞群的5%至20%，其数量与神经元一样多。小胶质细胞的一个关键功能是能够产生显著的先天和适应性免疫反应。小胶质细胞参与中枢神经系统的一线先天免疫。适当的抗原呈递对于适应性免疫系统产生特异性、持久的应答至关重要，需要T细胞受体与抗原呈递细胞在主要组织相容性复合体（MHC）分子上呈递的加工抗原肽之间的相互作用。小胶质细胞在中枢神经系统免疫中也有很大的调节作用。胶质瘤组织的组织病理学研究一致显示高水平的浸润性小胶质细胞。小胶质细胞也弥漫性地分布于整个肿瘤，而不是坏死区域，并且未观察到小胶质细胞吞噬胶质瘤细胞或碎片。最近的证据表明，浸润胶质瘤的小胶质细胞/巨噬细胞可能通过促进肿瘤微环境的免疫抑制来促进肿瘤生长。当被激活时，小胶质细胞可以是有效的免疫效应细胞，能够执行广泛的功能，并且在中枢神经系统损伤和疾病期间介导先天和适应性反应，同时在稳定状态下保持静止。它们在弥合免疫特权中枢神经系统和外周免疫系统之间的差距方面的多功能性，以及它们在胶质瘤中的显著数量，使它们成为胶质瘤免疫治疗中有吸引力的候选者。增强对小胶质瘤-胶质瘤相互作用的理解可以提供更好的方法来操纵胶质瘤微环境，从而产生特异性和持久的抗胶质瘤免疫。讨论了小胶质细胞在中枢神经系统免疫中的作用，重点介绍了胶质瘤免疫学的关键进展。
The central nervous system (CNS) historically has been considered an immune-privileged organ, lacking a lymphatic system and shielded from the circulatory system by the blood-brain barrier. Microglia are an abundant portion of the CNS cell population, comprising 5% to 20% of the total glial cell population, and are as numerous as neurons. A crucial function of microglia is the ability to generate significant innate and adaptive immune responses. Microglia are involved in first line innate immunity of the CNS. Proper antigen presentation is critical in the generation of specific, durable responses by the adaptive immune system, and requires interaction between the T cell receptor and processed antigen peptide presented on major histocompatibility complex (MHC) molecules by the antigen presenting cells. Microglia also have a large regulatory role in CNS immunity. Histopathologic studies of glioma tissue have consistently shown high levels of infiltrating microglia. Microglia are also localized diffusely throughout the tumor, rather than to the areas of necrosis, and phagocytosis of glioma cells or debris by microglia is not observed. Recent evidence indicates that glioma-infiltrating microglia/macrophages might be promoting tumor growth by facilitating immunosuppression of the tumor microenvironment. When activated, microglia can be potent immune effector cells, able to perform a broad range of functions, and they mediate both innate and adaptive responses during CNS injury and disease while remaining quiescent in the steady state. Their versatility in bridging the gap between the immune-privileged CNS and the peripheral immune system, in addition to their significant numbers in gliomas, makes them an attractive candidate in immunotherapy for gliomas. An enhanced understanding of microglia–glioma interaction can provide better methods to manipulate the glioma microenvironment to allow the generation of a specific and durable anti-glioma immunity. The role of microglia in CNS immunity is discussed, with a focus on key advances made in glioma immunology.
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