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Fas has a crucial role in the progression of experimental autoimmune encephalomyelitis
Y Okuda1, C C Bernard, H Fujimura
1Department of Neurology, Osaka University Medical School, Suita, Japan.
Abstract:
To investigate the role of Fas in experimental autoimmune encephalomyelitis (EAE) in mice, we examined the susceptibility of EAE in C57BL/6 (B6).lpr mice lacking Fas. The frequency of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in B6.lpr mice was significantly lower than that in B6 mice (19% vs 94%). However, no significant difference was observed between them in either the lymphocyte proliferation response or antibody reactivity to MOG. In addition, the histological examination and semiquantitative reverse transcriptase polymerase chain reaction analysis revealed that the infiltration of inflammatory cells and the up-regulation of gene expression for inflammatory cytokines occurred in the central nervous system (CNS) of B6.lpr mice immunized with MOG, even if they showed no clinical sign. These results indicate that Fas may contribute to the pathogenesis of EAE and may play a crucial role in the expansion of inflammation and/or myelin destruction in the CNS rather than in the activation of encephalitogenic T cells in the periphery and/or the breakdown of blood brain barrier.
Insights
Mice lacking Fas showed reduced experimental autoimmune encephalomyelitis (EAE) susceptibility. Fas appears crucial for central nervous system inflammation and myelin damage in EAE, not peripheral T cell activation.
Area of Science:
- Immunology
- Neuroscience
- Pathology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis.
- The role of Fas, a cell surface receptor involved in apoptosis, in EAE pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of Fas in the development and progression of EAE in mice.
- To determine if Fas deficiency affects the activation of encephalitogenic T cells or central nervous system (CNS) inflammation.
Main Methods:
- Comparison of EAE susceptibility in C57BL/6 (B6).lpr mice (lacking Fas) and wild-type B6 mice.
- Induction of EAE using myelin oligodendrocyte glycoprotein (MOG).
- Assessment of clinical signs, lymphocyte proliferation, antibody reactivity, CNS histology, and inflammatory cytokine gene expression.
Main Results:
- B6.lpr mice exhibited significantly lower EAE frequency (19%) compared to B6 mice (94%).
- No significant differences in MOG-specific lymphocyte proliferation or antibody responses were found between groups.
- CNS histological examination and gene expression analysis revealed inflammatory cell infiltration and increased inflammatory cytokine expression in MOG-immunized B6.lpr mice, despite the absence of clinical signs.
Conclusions:
- Fas plays a critical role in the pathogenesis of EAE.
- Fas is important for the expansion of inflammation and/or myelin destruction within the CNS during EAE.
- Fas's role is more significant in CNS pathology than in peripheral T cell activation or blood-brain barrier breakdown.