Endogenous type I interferons and their regulators in multiple sclerosis

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 .