School of Life and Environmental Sciences and the Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Front Immunol. 2023 Feb 3;14:1110593. doi: 10.3389/fimmu.2023.1110593. eCollection 2023.
Since their original discovery, type I interferons (IFN-Is) have been closely associated with antiviral immune responses. However, their biological functions go far beyond this role, with balanced IFN-I activity being critical to maintain cellular and tissue homeostasis. Recent findings have uncovered a darker side of IFN-Is whereby chronically elevated levels induce devastating neuroinflammatory and neurodegenerative pathologies. The underlying causes of these 'interferonopathies' are diverse and include monogenetic syndromes, autoimmune disorders, as well as chronic infections. The prominent involvement of the CNS in these disorders indicates a particular susceptibility of brain cells to IFN-I toxicity. Here we will discuss the current knowledge of how IFN-Is mediate neurotoxicity in the brain by analyzing the cell-type specific responses to IFN-Is in the CNS, and secondly, by exploring the spectrum of neurological disorders arising from increased IFN-Is. Understanding the nature of IFN-I neurotoxicity is a crucial and fundamental step towards development of new therapeutic strategies for interferonopathies.
自最初发现以来，I 型干扰素（IFN-Is）就与抗病毒免疫反应密切相关。然而，它们的生物学功能远不止于此，平衡的 IFN-I 活性对于维持细胞和组织的内稳态至关重要。最近的研究发现 IFN-Is 具有阴暗的一面，即慢性高水平 IFN-Is 会引发破坏性的神经炎症和神经退行性病变。这些“干扰素病”的潜在原因多种多样，包括单基因综合征、自身免疫性疾病以及慢性感染。这些疾病中中枢神经系统的突出受累表明脑细胞对 IFN-I 毒性特别敏感。在这里，我们将通过分析中枢神经系统中 IFN-Is 的细胞类型特异性反应，以及探讨由 IFN-Is 增加引起的神经障碍谱，来讨论目前关于 IFN-Is 如何在大脑中介导神经毒性的知识。了解 IFN-I 神经毒性的性质是开发干扰素病新治疗策略的关键和基础步骤。
