2'-5' oligoadenylate synthetase-like 1 (OASL1) deficiency suppresses central nervous system damage in a murine MOG-induced multiple sclerosis model.
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.
Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
Bo Young
BY
Choi
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.
Chan Kyu
CK
Sim
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.
Yeon Sook
YS
Cho
Department of Nursing, Inha University, Incheon, Republic of Korea.
Min
M
Sohn
Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul 120-749, Republic of Korea.
Young-Joon
YJ
Kim
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. Electronic address: myeong@amc.seoul.kr.
Myeong Sup
MS
Lee
Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea. Electronic address: swsuh@hallym.ac.kr.
Sang Won
SW
Suh
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002531:Cerebellum / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D005260:Female; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism
D063308:Myelin-Oligodendrocyte Glycoprotein; C475083:Oasl1 protein, mouse; D015088:2',5'-Oligoadenylate Synthetase
CNS inflammation; Experimental autoimmune encephalomyelitis; Multiple sclerosis; OASL1; Type I interferon negative regulator