Article

Primary oligodendrocyte death does not elicit anti-CNS immunity.

Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
Nature Neuroscience (Impact Factor: 15.25). 02/2012; 15(4):543-50. DOI: 10.1038/nn.3062
Source: PubMed

ABSTRACT Anti-myelin immunity is commonly thought to drive multiple sclerosis, yet the initial trigger of this autoreactivity remains elusive. One of the proposed factors for initiating this disease is the primary death of oligodendrocytes. To specifically test such oligodendrocyte death as a trigger for anti-CNS immunity, we inducibly killed oligodendrocytes in an in vivo mouse model. Strong microglia-macrophage activation followed oligodendrocyte death, and myelin components in draining lymph nodes made CNS antigens available to lymphocytes. However, even conditions favoring autoimmunity-bystander activation, removal of regulatory T cells, presence of myelin-reactive T cells and application of demyelinating antibodies-did not result in the development of CNS inflammation after oligodendrocyte death. In addition, this lack of reactivity was not mediated by enhanced myelin-specific tolerance. Thus, in contrast with previously reported impairments of oligodendrocyte physiology, diffuse oligodendrocyte death alone or in conjunction with immune activation does not trigger anti-CNS immunity.

0 Bookmarks
 · 
188 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroinflammation is the foremost defense reaction of the nervous system to most if not all insults. Injuries to the central and peripheral nervous system (CNS and PNS) are followed by immediate activation of innate immune cells and infiltration of peripheral immune cells, amid waves of upregulation of numerous inflammatory mediators. Prolonged inflammation can lead to secondary tissue damage and prohibit regeneration of the injured nervous system. The regulation of inflammation and neuroregeneration are orchestrated through a complex network of signal transduction. Interestingly, many molecules play pleiotropic roles in both processes. Growing evidence implicates a handful of axon regeneration regulators in the processes of neuroinflammation, among which are the myelin and glial scar associated axon growth inhibitors and their axonal receptors. In this article, we will review the roles of these canonical axon regeneration regulators in neuroinflammation.
    Experimental Neurology. 01/2014; 258:17–23.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon-myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a local inflammatory disease process early in MS into the global progressive disorder seen during later stages. This mode of spreading could also apply to other neurological disorders.
    The Journal of Cell Biology 08/2014; 206(3):335-345. · 10.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: SUMMARY Healthy oligodendrocytes are crucial for neurons and abnormal functioning of these cells is involved in several neurodegenerative diseases. We will focus on oligodendroglial pathology in amyotrophic lateral sclerosis (ALS), an adult-onset progressive neurodegenerative disease characterized by selective motor neuron loss. Recent discoveries shed new light on the crucial role of oligodendrocytes in this fatal disease. We will first give an overview of the importance of good-functioning oligodendrocytes for neuronal health, in particular for motor neurons. Subsequently, we will discuss the recent data on oligodendroglial abnormalities in ALS. We conclude that oligodendrocytes should be considered as important contributors to motor neuron degeneration. As a consequence, oligodendrocytes are a promising new therapeutic target for ALS and other neurodegenerative diseases.
    Neurodegenerative disease management. 06/2014; 4(3):223-39.

Similar Publications