Metabolism and autophagy in the immune system: immunometabolism comes of age.
Metabolism and autophagy in the immune system: immunometabolism comes of age.
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DOI：
10.1111/j.1600-065x.2012.01158.x
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发表时间：
2012-09
影响因子：
8.7
通讯作者：
Rathmell JC
中科院分区：
文献类型：
--
作者：
Rathmell JC
细胞和动物与环境相互作用的两种最基本的方式是通过获取足够维持生命的营养物质和防御潜在致病生物的攻击。因此，免疫细胞的新陈代谢和功能是联系在一起的，免疫系统作为一个整体与基本的代谢组织和过程联系在一起并密切相互作用，这一点也就不足为奇了。这一基本前提现在被广泛接受，但直到最近，在免疫系统研究和营养和新陈代谢研究中，这一基本前提都被忽视了。然而，近一百年前很明显，营养和免疫状态可能相关，因为营养不良被明确定义为一种免疫抑制状况，在营养不良人群中感染增加(1，2)。从进化上看，似乎高度依赖能量的免疫保护过程被简单地选择为一个在饥荒时期迅速牺牲的系统，以保持足够的能量来维持立即重要的功能，如神经和心血管系统。这种营养和免疫关联现在为免疫新陈代谢作为一个领域的兴起提供了背景。目前的想法承认，免疫和新陈代谢之间的联系不仅限于营养不良，还包括基本的细胞过程以及免疫细胞和新陈代谢组织之间的密切相互作用。特别是，免疫反应是高度依赖能量的，淋巴细胞如何获得能量为调节免疫和定义特定的免疫功能提供了一种新的途径。代谢应激反应途径，如自噬，也与免疫密切相关，可以激活先天免疫反应，允许适应性免疫，以及直接消除一些病原体。此外，西方世界日益增长的肥胖症和代谢综合征现在被认为是炎症和过度免疫作为病理的根源。随着对这些区域重要性的认识日益加深，免疫代谢领域现在对免疫的基本生物学理解以及在各种病理环境中都具有广泛的重要性。这一卷包括讨论这些主题中每一个的当前文献和思想的综述，并指出未来的方向，如何最终利用代谢与免疫的联系来治疗广泛的代谢和免疫学疾病。
Two of the most fundamental ways in which cells and animals interact with their environment are through obtaining nutrients sufficient to sustain life and defending against attack of potentially pathogenic organisms. It is not surprising with some reflection, therefore, that immune cell metabolism and function are linked and that the immune system as a whole is connected and closely interacts with basic metabolic tissues and processes. This basic premise is now well accepted, but, until recently, was overlooked in both studies of the immune system and in studies of nutrition and metabolism. It had been apparent nearly one hundred years ago, however, that nutrition and immunological state could be associated, as malnutrition was clearly defined as an immunosuppressive condition, with increased infections in poorly fed populations (1, 2). Evolutionarily, it appears that the highly energy-dependent process of immune protection was simply selected as a system to be quickly sacrificed in times of famine, so as to maintain enough energy for immediately vital functions, such as neuronal and cardiovascular systems.This nutrition and immunity association now provides context for the rise of immunometabolism as a field. Current thinking acknowledges that the links between immunity and metabolism are not limited to malnutrition and include basic cellular processes as well as close interactions between immune cells and metabolic tissues. In particular, immune responses are highly energy dependent, and how lymphocytes obtain their energy offers a new approach to modify immunity and define specific immune functions. Metabolic stress response pathways, such as autophagy, are also intimately tied to immunity, to activate the innate immune response, to allow adaptive immunity, as well as to directly eliminate some pathogens. In addition, the growing incidence of obesity and the metabolic syndrome in the western world are now known to have inflammation and overactive immunity as a root source of pathology. As recognition of the importance of these areas grows, the field of immunometabolism is now of broad importance in basic biologic understanding of immunity as well as in a variety of pathological settings. This volume includes reviews to discuss current literature and thought on each of these topics and to point toward future directions how metabolic links with immunity ultimately may be exploited to treat a wide array of metabolic and immunologic diseases.