Choi Bo Young, Sim Chan Kyu, Cho Yeon Sook, Sohn Min, Kim Young-Joon, Lee Myeong Sup, Suh Sang Won
Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
Laboratory of Molecular Immunology and Medicine (MoIM), Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
Neurosci Lett. 2016 Aug 15;628:78-84. doi: 10.1016/j.neulet.2016.06.026. Epub 2016 Jun 11.
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.
I型干扰素（IFN-I）对于抗病毒和抗肿瘤防御至关重要。此外，IFN-I已被用于治疗多发性硬化症（MS），这是一种中枢神经系统（CNS）的慢性自身免疫性疾病。最近，我们报道2'-5'寡腺苷酸合成酶样1（OASL1）在病毒感染和肿瘤攻击时负向调节IFN-I的产生。因此，OASL1缺陷（Oasl1(-)(/)(-)）小鼠对病毒感染和肿瘤攻击具有抗性。在本研究中，我们通过使用Oasl1(-)(/)(-)小鼠和小鼠MS模型，即髓鞘少突胶质细胞糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE），来研究OASL1在自身免疫性MS发展中是否起负向作用。与野生型（WT）小鼠相比，Oasl1(-)(/)(-)小鼠对EAE发展表现出更强的抗性。此外，与WT小鼠相比，EAE诱导的Oasl1(-)(/)(-)小鼠中枢神经系统中浸润的免疫细胞如T细胞和巨噬细胞较少，中枢神经系统炎症也较少。总体而言，这些结果表明OASL1缺陷抑制了MS样自身免疫的发展，并提示IFN-I的负调节因子可能是治疗人类MS的良好治疗靶点。
