The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain.
The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain.
复制标题
DOI：
10.3389/fimmu.2014.00136
复制
发表时间：
2014
影响因子：
7.3
通讯作者：
Rivest S
中科院分区：
文献类型：
--
作者：
Bellavance MA;Rivest S
为了应对生理和心理应激，下丘脑-垂体-肾上腺（HPA）轴协调糖皮质激素（GC）的全身释放。由于GC受体几乎无处不在的表达和GC的多方面代谢、心血管、认知和免疫功能，该系统在应激反应和稳态恢复中起着至关重要的作用。GC作用于几乎所有类型的免疫细胞，并且长期以来被认为通过各种基因组和非基因组机制执行显著的免疫抑制和抗炎功能。类固醇激素的这些著名作用在过去70年中已在临床中得到利用，合成GC衍生物通常用于治疗各种过敏性、自身免疫性、炎症性和血液学疾病。然而，HPA轴和GC在抑制整个生物体的免疫反应中的作用仍然存在争议，因为越来越多的证据表明GC在特定条件下也可以对免疫系统产生许可和刺激作用。GC的这种自相矛盾的作用在大脑中特别明显，大量数据支持类固醇激素的有益或有害作用。在这篇综述中，我们研究了GC对先天免疫系统的作用，特别关注CNS区室。我们还剖析了众多的分子机制，通过GC发挥其作用，并讨论了各种参数影响的矛盾免疫调节功能的GC在大脑中。
In response to physiological and psychogenic stressors, the hypothalamic–pituitary–adrenal (HPA) axis orchestrates the systemic release of glucocorticoids (GCs). By virtue of nearly ubiquitous expression of the GC receptor and the multifaceted metabolic, cardiovascular, cognitive, and immunologic functions of GCs, this system plays an essential role in the response to stress and restoration of an homeostatic state. GCs act on almost all types of immune cells and were long recognized to perform salient immunosuppressive and anti-inflammatory functions through various genomic and non-genomic mechanisms. These renowned effects of the steroid hormone have been exploited in the clinic for the past 70 years and synthetic GC derivatives are commonly used for the therapy of various allergic, autoimmune, inflammatory, and hematological disorders. The role of the HPA axis and GCs in restraining immune responses across the organism is however still debated in light of accumulating evidence suggesting that GCs can also have both permissive and stimulatory effects on the immune system under specific conditions. Such paradoxical actions of GCs are particularly evident in the brain, where substantial data support either a beneficial or detrimental role of the steroid hormone. In this review, we examine the roles of GCs on the innate immune system with a particular focus on the CNS compartment. We also dissect the numerous molecular mechanisms through which GCs exert their effects and discuss the various parameters influencing the paradoxical immunomodulatory functions of GCs in the brain.