Type I interferon pathway in CNS homeostasis and neurological disorders.

Abstract

Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS). Furthermore, IFNs can reach the CNS from the periphery to modulate the function of not only microglia and astrocytes, but also neurons and oligodendrocytes, with major consequences for cognition and behavior. Given the pleiotropic nature of type I IFNs, it is critical to determine their exact cellular impact. Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed "interferonopathies" including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency. In contrast, in the CNS of mice with virus-induced neuroinflammation, type I IFNs can limit production of other cytokines to prevent potential damage associated with chronic cytokine expression. This capacity of type I IFNs could also explain the therapeutic benefits of exogenous type I IFN in chronic CNS autoimmune diseases such as multiple sclerosis. In this review we will highlight the importance of a well-balanced level of type I IFNs for healthy brain physiology, and to what extent dysregulation of this cytokine system can result in brain 'interferonopathies'.

• Authors: Thomas Blank, Marco Prinz
• Journal: Glia (Glia) Vol. 65 Issue 9 Pg. 1397-1406 (09 2017) ISSN: 1098-1136 [Electronic] United States
• PMID: 28519900 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Interferon Type I

Topics

• Animals
• Central Nervous System (metabolism)
• Homeostasis (physiology)
• Humans
• Interferon Type I (metabolism)
• Nervous System Diseases (metabolism)