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GRIM-19 Ameliorates Multiple Sclerosis in a Mouse Model of Experimental Autoimmune Encephalomyelitis with Reciprocal Regulation of IFNγ/Th1 and IL-17A/Th17 Cells

  • Jeonghyeon Moon (Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea) ;
  • Seung Hoon Lee (Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Seon-yeong Lee (Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Jaeyoon Ryu (Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Jooyeon Jhun (Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • JeongWon Choi (Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Gyoung Nyun Kim (College of Medicine, The Catholic University of Korea) ;
  • Sangho Roh (Cellular Reprogramming and Embryo Biotechnology Laboratory, Dental Research Institute, BK21 PLUS Dental Life Science, Seoul National University School of Dentistry) ;
  • Sung-Hwan Park (Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Mi-La Cho (Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea)
  • Received : 2020.07.22
  • Accepted : 2020.09.23
  • Published : 2020.10.31
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Abstract

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI20C1496) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C3062).

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