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Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis
Fernanda Chiuso-Minicucci1, Larissa Lumi Watanabe Ishikawa1, Luiza Ayumi Nishiyama Mimura1
1Department of Microbiology and Immunology, Biosciences Institute, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Abstract:
Experimental autoimmune encephalomyelitis (EAE) is an animal model to study multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with active vitamin D in EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG emulsified with Complete Freund's Adjuvant plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses of Bordetella pertussis toxin. One day after immunization, mice were treated with 0,1 μg of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150 μg) was co-administered on days 3 and 11. The administration of 1,25(OH)2D3 or MOG determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with 1,25(OH)2D3 the animals did not develop EAE. Spleen and central nervous system (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation with MOG in comparison to the EAE control group. In addition, this treatment inhibited dendritic cells maturation in the spleen and reduced inflammatory infiltration in the CNS. The association of MOG with 1,25(OH)2D3 was able to control EAE development.
Insights
Active vitamin D combined with myelin oligodendrocyte glycoprotein effectively prevented experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. This combination therapy reduced disease severity and key inflammatory markers in mice.
Area of Science:
- Neuroimmunology
- Endocrinology
Background:
- Experimental autoimmune encephalomyelitis (EAE) serves as a crucial animal model for studying multiple sclerosis (MS).
- Active vitamin D is known for its immunomodulatory and tolerogenic properties.
- Myelin oligodendrocyte glycoprotein (MOG) is a key autoantigen in EAE.
Purpose of the Study:
- To investigate the therapeutic potential of combining MOG with active vitamin D (1α,25-dihydroxyvitamin D3 or 1,25(OH)2D3) in preventing EAE development.
- To assess the impact of this combination therapy on clinical disease progression, immune cell responses, and central nervous system (CNS) inflammation.
Main Methods:
- EAE was induced in female C57BL/6 mice using MOG immunization.
- Mice received 1,25(OH)2D3 every other day and MOG on specific days.
- Clinical scores, EAE incidence, cytokine production (IL-6, IL-17), dendritic cell maturation, and CNS inflammatory infiltration were evaluated.
Main Results:
- Administration of 1,25(OH)2D3 or MOG alone significantly reduced EAE incidence and clinical scores.
- The co-administration of MOG with 1,25(OH)2D3 completely prevented EAE development in mice.
- This combination therapy suppressed MOG-induced IL-6 and IL-17 production, inhibited dendritic cell maturation, and reduced CNS inflammatory infiltration.
Conclusions:
- The combination of MOG and 1,25(OH)2D3 demonstrates potent therapeutic efficacy in controlling EAE.
- This novel therapeutic strategy holds promise for the management of multiple sclerosis by modulating immune responses and reducing neuroinflammation.
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