Multiple sclerosis: immune system molecule expression in the central nervous system
1Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
Insights
Multiple sclerosis (MS) involves central nervous system (CNS) inflammation with immune cells expressing molecules similar to peripheral tissues. However, the CNS shows poor repair due to its complexity and vulnerability, impacting oligodendrocyte and myelin health.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Inflammation
- Multiple Sclerosis (MS) Pathogenesis
Background:
- The central nervous system (CNS) interacts with the lymphoid system during inflammation, primarily via induced expression of immune molecules on CNS elements.
- CNS endothelium, astrocytes, and microglial cells are key players, while oligodendrocytes and neurons are largely unaffected.
- The molecular responses in the CNS during inflammation resemble those in peripheral lymphoid tissues.
Purpose of the Study:
- To analyze the immunologic and immunopathologic mechanisms underlying inflammation in the brain and spinal cord in multiple sclerosis (MS).
- To explore the reasons for the poor reparatory response in the CNS following inflammatory insults.
- To present potential therapeutic strategies for preventing or reducing CNS inflammation in MS, drawing from experimental models.
Main Methods:
- Immunologic and immunopathologic analyses of the brain and spinal cord.
- Comparison of molecular markers expressed during CNS inflammation with those in peripheral lymphoid tissue.
- Utilizing experimental allergic encephalomyelitis (EAE) as a model for MS to evaluate therapeutic approaches.
Main Results:
- CNS inflammation involves interactions with the lymphoid system through induced expression of immune molecules on CNS cells.
- Molecular markers in CNS inflammation are similar to peripheral tissues, but the outcome differs due to poor CNS repair.
- Reasons for poor repair include CNS anatomical complexity, vulnerability to mediators, and oligodendrocyte/myelin sensitivity.
Conclusions:
- The CNS mounts an inflammatory response involving specific cell types and molecular signaling pathways.
- Poor CNS repair in MS is attributed to structural factors and the sensitivity of white matter components.
- Therapeutic strategies targeting CNS inflammation, informed by EAE models, offer potential avenues for MS treatment.
Abstract:
The fundamental message emerging from immunologic and immunopathologic analyses of the brain and spinal cord in multiple sclerosis (MS) is that during inflammation, the central nervous system (CNS) is capable of interactions with the lymphoid system, mainly through induced (as opposed to constitutive) expression of immune system-specific molecules on CNS elements. CNS endothelium, astrocytes and microglial cells are the main participants, with oligodendrocytes and neurons remaining essentially inert. There appears to be nothing unique about the manner in which the CNS responds to inflammation or in the molecules expressed. The ensuing adhesion molecules, pro-inflammatory and regulatory cytokines, histocompatibility molecules, and T and B cell markers, are difficult to distinguish from those occurring in peripheral lymphoid tissue. However, differences certainly exist in the outcome of an inflammatory insult in the CNS versus other, peripheral tissues, whereby there is generally a poor reparatory response. Reasons for the latter appear to lie in the anatomical complexity of the CNS, its vulnerability to damage by soluble mediators, and in the white matter (the battlefield for the inflammatory attack in MS), the exquisite sensitivity of the oligodendrocyte and its myelin to exogenous factors. With the aid of examples drawn from experimental allergic encephalomyelitis, the prime animal model for MS, a number of approaches to prevent or downregulate CNS inflammation during immune-mediated demyelination are presented as possible therapeutic avenues for MS, some of which are already under investigation.
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