Endogenous type I interferons and their regulators in multiple sclerosis

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• 作者：Yusei Miyazaki and Masaaki Niino
• 刊名：Clinical and Experimental Neuroimmunology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：8
• 期：S1
• 页码：17-23
• 全文大小：116K
• ISSN：1759-1961

文摘

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. In the past few decades, several disease-modifying drugs including interferon (IFN)-β have become available for treating MS. IFN-β belongs to the type I IFN family, and thus is an endogenous molecule whose primary role is thought to be host defense against viruses. In addition, type I IFN are constitutively produced at low amounts and involved in the homeostasis of various tissues. In contrast, it is suggested that type I IFN play a pathogenic role in other autoimmune diseases, such as lupus. Several lines of evidence from studies using MS samples and animal models suggest the protective role of endogenous type I IFN in MS. Correspondingly, MS patients with a higher endogenous type I IFN signature show lower disease activity. Paradoxically, these patients have been shown to respond poorly to IFN-β therapy. In addition, an animal model with a defective regulatory mechanism in type I IFN signaling has been shown to develop augmented central nervous system autoimmunity, suggesting that type I IFN responses need to be appropriately regulated in MS. Multiple endogenous molecules participate in the regulation of type I IFN responses, but their roles in MS have not been studied extensively. Further study delineating the role of endogenous type I IFN and their regulatory mechanisms in MS should enhance our understanding of the disease, and could lead to improvements in the therapeutic effects of IFN-β in MS.