Oligodendrocyte Precursor Cell-Specific HMGB1 Knockout Reduces Immune Cell Infiltration and Demyelination in Experimental Autoimmune Encephalomyelitis Models.
10.1007/s12264-025-01381-9
- Author:
Gyuree KIM
1
;
JiHye SEO
1
;
Bokyung KIM
1
;
Young-Ho PARK
2
;
Hong Jun LEE
3
;
Fuzheng GUO
4
;
Dong-Seok LEE
5
Author Information
1. BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
2. Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea.
3. College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
4. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
5. BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea. lee1@knu.ac.kr.
- Publication Type:Journal Article
- Keywords:
Experimental autoimmune encephalomyelitis;
High mobility group box 1;
Multiple sclerosis;
Oligodendrocyte precursor cell
- MeSH:
Animals;
Encephalomyelitis, Autoimmune, Experimental/metabolism*;
HMGB1 Protein/deficiency*;
Mice, Knockout;
Oligodendrocyte Precursor Cells/immunology*;
Mice, Inbred C57BL;
CD4-Positive T-Lymphocytes/immunology*;
Cell Movement;
Blood-Brain Barrier/immunology*;
Mice;
Myelin Sheath/pathology*;
Disease Models, Animal;
Coculture Techniques;
Oligodendroglia/metabolism*;
Female;
Cells, Cultured
- From:
Neuroscience Bulletin
2025;41(7):1145-1160
- CountryChina
- Language:English
-
Abstract:
Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model, experimental autoimmune encephalomyelitis (EAE). This study investigates the role of high mobility group box 1 (HMGB1) in oligodendrocyte precursor cells (OPCs) in modulating pathogenic T cells infiltrating the central nervous system through the blood-brain barrier (BBB) by using OPC-specific HMGB1 knockout (KO) mice. We found that HMGB1 released from OPCs promotes BBB disruption, subsequently allowing increased immune cell infiltration. The migration of CD4+ T cells isolated from EAE-induced mice was enhanced when co-cultured with OPCs compared to oligodendrocytes (OLs). OPC-specific HMGB1 KO mice exhibited lower BBB permeability and reduced immune cell infiltration into the CNS, leading to less damage to the myelin sheath and mitigated EAE progression. CD4+ T cell migration was also reduced when co-cultured with HMGB1 knock-out OPCs. Our findings reveal that HMGB1 secretion from OPCs is crucial for regulating immune cell infiltration and provides insights into the immunomodulatory function of OPCs in autoimmune diseases.
