UMR 7242 Biotechnologie et Signalisation Cellulaire, École Supérieure de Biotechnologie de Strasbourg (ESBS), Laboratoire d'Excellence Médalis, Université de Strasbourg/CNRS, 67412 Illkirch, France.
ICube UMR 7357, Université de Strasbourg/CNRS, Fédération de Médecine Translationnelle de Strasbourg, 67000 Strasbourg, France.
Int J Mol Sci. 2018 Nov 13;19(11):3588. doi: 10.3390/ijms19113588.
It took decades to arrive at the general consensus dismissing the notion that the immune system is independent of the central nervous system. In the case of uncontrolled systemic inflammation, the relationship between the two systems is thrown off balance and results in cognitive and emotional impairment. It is specifically true for autoimmune pathologies where the central nervous system is affected as a result of systemic inflammation. Along with boosting circulating cytokine levels, systemic inflammation can lead to aberrant brain-resident immune cell activation, leakage of the blood⁻brain barrier, and the production of circulating antibodies that cross-react with brain antigens. One of the most disabling autoimmune pathologies known to have an effect on the central nervous system secondary to the systemic disease is systemic lupus erythematosus. Its neuropsychiatric expression has been extensively studied in lupus-like disease murine models that develop an autoimmunity-associated behavioral syndrome. These models are very useful for studying how the peripheral immune system and systemic inflammation can influence brain functions. In this review, we summarize the experimental data reported on murine models developing autoimmune diseases and systemic inflammation, and we explore the underlying mechanisms explaining how systemic inflammation can result in behavioral deficits, with a special focus on in vivo neuroimaging techniques.
花了几十年的时间才达成普遍共识，摒弃了免疫系统独立于中枢神经系统的观点。在系统性炎症失控的情况下，这两个系统之间的关系失去平衡，导致认知和情绪障碍。在自身免疫性疾病中尤其如此，因为系统性炎症会导致中枢神经系统受到影响。除了提高循环细胞因子水平外，系统性炎症还会导致异常的脑驻留免疫细胞激活、血脑屏障渗漏以及产生与脑抗原发生交叉反应的循环抗体。系统性红斑狼疮是已知的一种会对中枢神经系统造成影响的自身免疫性疾病，它的神经精神表现已在狼疮样疾病的小鼠模型中得到了广泛研究，这些模型会发展出自发性免疫相关的行为综合征。这些模型对于研究外周免疫系统和系统性炎症如何影响大脑功能非常有用。在这篇综述中，我们总结了报道的在发生自身免疫性疾病和系统性炎症的小鼠模型中的实验数据，并探讨了可以解释系统性炎症如何导致行为缺陷的潜在机制，特别关注了体内神经影像学技术。
