Oligodendrocyte Precursor Cell-Specific HMGB1 Knockout Reduces Immune Cell Infiltration and Demyelination in Experimental Autoimmune Encephalomyelitis Models
Gyuree Kim1,2 · JiHye Seo1,2 · Bokyung Kim1,2,3 · Young‑Ho Park4 · Hong Jun Lee5,6 · Fuzheng Guo7,8 · Dong‑Seok Lee1,21 BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
2 School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
3 Illimis Therapeutics, Inc., Seoul 06376, Republic of Korea
4 Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea
5 College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
6 Research Institute, huMetaCELL Inc., 220 Bugwang-ro, Bucheon-si, Gyeonggi-do 14786, Republic of Korea
7 Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA 95817, USA
8 Department of Neurology, School of Medicine, University of California, Davis, Davis, CA 95817, USA
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.
Keywords
Multiple sclerosis; High mobility group box 1; Oligodendrocyte precursor cell; Experimental autoimmune encephalomyelitis
