2′-5′ oligoadenylate synthetase-like 1 (OASL1) deficiency suppresses central nervous system damage in a murine MOG-induced multiple sclerosis model. (15th August 2016)

• Record Type: Journal Article
• Authors: Choi, Bo Young; Sim, Chan Kyu; Cho, Yeon Sook; Sohn, Min; Kim, Young-Joon; Lee, Myeong Sup; Suh, Sang Won
• Is Part Of: Neuroscience letters. Volume 628(2016)
• Page Start: 78
• Page End: 84
• Publication Date: 2016-08-15
• Subjects: OASL1 -- Experimental autoimmune encephalomyelitis -- Multiple sclerosis -- CNS inflammation -- Type I interferon negative regulator; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.06.026
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: IFN-I negative regulator gene Oasl1 − /− mice are more resistant to EAE development. EAE-induced Oasl1 − / − mice have fewer infiltrated pathogenic immune cells in the CNS. EAE-induced Oasl1 − / − mice show less CNS inflammation, compared to wild-type mice. EAE-induced Oasl1 − / − mice contain tighter blood-brain barrier. Thus, IFN-I negative regulators could be therapeutic targets for multiple sclerosis. Abstract: Type I Interferon (IFN-I) is critical for antiviral and antitumor defense. Additionally, IFN-I has been used for treating multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system (CNS). Recently, we reported that 2′-5′ oligoadenylate synthetase-like 1 (OASL1) negatively regulates IFN-I production upon viral infection and tumor challenge. Therefore, OASL1 deficient ( Oasl1 − / − ) mice are resistant to viral infections and tumor challenge. In this study, we examined whether OASL1 plays a negative role in the development of autoimmune MS by using Oasl1 − / − mice and a murine MS model, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). Oasl1 − / − mice showed enhanced resistance to EAE development compared to wild-type (WT) mice. Additionally, EAE-induced Oasl1 − / − mice showed fewer infiltrated immune cells such as T cells and macrophages in the CNS and less CNS inflammation, compared to WT mice. Collectively, these results indicate that OASL1 deficiency suppresses the development of MS-like autoimmunity and suggest that negative regulators of IFN-I could be good therapeutic targets for treating MS in humans.