The Protective Role of Interferon-gamma in CNS Autoimmunity

Date

2013

Authors

Sosa, Rebecca A.

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Volume Title

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Abstract

Multiple Sclerosis (MS) is the most common autoimmune disease of the central nervous system. Increases in the "pro-inflammatory" cytokine interferon-gamma (IFN-ɣ) have been identified in the cerebrospinal fluid (CSF) and lesions of MS patients, however it is not well understood what its specific role there might be. It is well known that IFN-ɣ activates antigen presenting cells to present myelin antigens to myelin-reactive T cells in the CNS during experimental autoimmune encephalomyelitis (EAE), a mouse model of human MS. Paradoxically, loss of IFN-ɣ signaling does not ameliorate disease as expected, but rather increases disease severity resulting in a chronic inflammatory state. Our data show that IFN-ɣ has an important protective role in EAE by promoting CNS-resident microglia to clean up myelin debris generated from demyelination of neuronal axons throughout the course of disease. We demonstrate that microglia are loaded with myelin antigen even in the naïve brain to perform this important function during normal maintenance of myelin sheaths and neuronal connections. Further, we show that myelin antigen release in the CNS can contribute to relapses similar to that seen in MS patients. Our long term goal is to better control the chronic inflammatory state that many MS patients progress to, and manipulating levels of IFN-ɣ at various stages of disease may be an important therapeutic strategy in the future.

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Keywords

EAE/MS, macrophage, microglia, myelin, neurodegeneration, neuroinflammation

Citation

Department

Integrative Biology