Type I interferon dysregulation and neurological disease

@article{McGlasson2015TypeII,
  title={Type I interferon dysregulation and neurological disease},
  author={Sarah L McGlasson and Alexa Jury and Andrew Jackson and David P J Hunt},
  journal={Nature Reviews Neurology},
  year={2015},
  volume={11},
  pages={515-523}
}
Type I interferon is an essential component of the brain's innate immune defence, conferring protection against viral infection. Recently, dysregulation of the type I interferon pathway has been implicated in the pathogenesis of a spectrum of neuroinfectious and neuroinflammatory disorders. Underactivity of the type I interferon response is associated with a predisposition to herpes simplex encephalitis. Conversely, a group of 'interferonopathic' disorders, characterized by severe… 
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Although IFN signaling is the top elevated pathway in nGD, it is demonstrated that this pathway is not related to mouse viability and is consequently defined as a secondary pathology pathway.
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It is found that under basal conditions, each cell type has a unique gene expression pattern reflective of its developmental origin and biological function, which suggests specialized roles for these cells in host defense and in the development of cerebral interferonopathy.
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How type-I and type-II IFNs regulate pain and infection via neuro-immune modulations, with special focus on neuroinflammation and neuro-glial interactions is discussed, and distinct roles of type- I IFNs in the peripheral and central nervous system are highlighted.
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Observations reveal an essential in vivo function of STAT2 in the regulation of human IFNα/β signaling, providing concrete evidence of the serious pathological consequences of unrestrained IFN α/β activity and supporting efforts to target this pathway therapeutically in IFN-associated disease.
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In the mouse model for IFN-I-induced neurodegeneration, protein phosphorylation, rather than the proteome, aligned with the clinical hallmarks and pathological outcome, including impaired development, motor dysfunction and seizures.
Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord
TLDR
It is observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I- IFN.
Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature.
TLDR
Clinical and experimental findings provide evidence of a causal link between type I IFN and TMA, and recombinant type IIFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation.
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