Interferons in the central nervous system: A few instruments play many tunes

@article{Owens2014InterferonsIT,
  title={Interferons in the central nervous system: A few instruments play many tunes},
  author={Trevor Owens and Reza Khorooshi and Agnieszka Wlodarczyk and Nasrin Asgari},
  journal={Glia},
  year={2014},
  volume={62}
}
Interferons (IFNs) are implicated as an important component of the innate immune system influencing viral infections, inflammation, and immune surveillance. We review here the complex biological activity of IFNs in the central nervous system (CNS) and associated glial–immune interactions, with focus specifically on the Type I IFNs in physiological and pathological conditions. IFN‐α and IFN‐β are the predominant Type I IFNs in the CNS. They are produced in the CNS by glial cells, mostly… 
Type I interferon pathway in CNS homeostasis and neurological disorders
TLDR
The importance of a well‐balanced level of type I IFNs for healthy brain physiology is highlighted, and to what extent dysregulation of this cytokine system can result in brain ‘interferonopathies’ is investigated.
Microglia responses to interleukin‐6 and type I interferons in neuroinflammatory disease
TLDR
Findational knowledge regarding the microglial response to IL‐6 and IFN‐I is now being used to devise therapeutic strategies to ameliorate neuroinflammation and promote repair: either through targeting microglia, or by targeting the reduction of CNS levels or downstream biological pathways of IL-6 or IFN-I.
Peli1 negatively regulates type I interferon induction and antiviral immunity in the CNS
TLDR
These results establish Peli1 as an innate immune regulator in the CNS that modulates the threshold of IFN-I responses against viral infections.
Chronic neurodegeneration induces type I interferon synthesis via STING, shaping microglial phenotype and accelerating disease progression
TLDR
STING‐dependent IFN‐I influences microglial phenotype and influences neurodegenerative progression despite occurring secondary to initial degenerative changes, expanding the mechanistic understanding of IFN-I induction and its impact on microglia function during chronic neurodegenersation.
Microglial Interferon Signaling and White Matter
TLDR
Recent studies implicate “microgliopathies” more broadly in neurological disorders including Alzheimer’s disease (AD) and MS, suggesting that microglia are a potential therapeutic target for disease prevention and/or treatment, with interferon signaling playing a key role in regulating the microglial phenotype.
Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis
TLDR
Results show that Type IIFN induced within the CNS can play a protective role in EAE and highlight the role of endogenous type I IFN in mediating neuroprotection.
IFNβ as regulator of CD14/TLR4-mediated microglial responses to CNS infection and damage
TLDR
How IFNβ differentially regulates microglial responses to CNS infection and damage is shown, which underlines that immunomodulatory effects of type I interferons are very specific and highlights the importance of understanding their mode of action.
Type I interferon‐activated microglia are critical for neuromyelitis optica pathology
TLDR
The data show a pro‐pathologic role for IFNI‐activated microglia in NMO and open new perspectives for microglial‐targeted therapies, and a strong IFNI footprint in affected CNS tissue as well as in microglian subpopulations.
Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer’s disease
TLDR
The role of Aim2/AIM2 proteins in the development of AD is discussed and an improved understanding of the role of Absent in Melanoma 2 proteins in AD could identify new approaches to treat patients.
Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity
TLDR
The current understanding of the origin, phenotype, and function of microglia and CNS immigrating macrophages in the pathogenesis of MS and EAE is reviewed and the emerging roles ofmicroglia as IFNβ-producing cells and vice versa are highlighted.
...
...

References

SHOWING 1-10 OF 218 REFERENCES
Antiviral Type I and Type III Interferon Responses in the Central Nervous System
TLDR
This review addresses some trends and recent developments concerning the role of type I and type III IFNs in preventing neuroinvasion and infection of CNS cells; the identity of IFN-producing cells in the CNS; the antiviral activity of ISGs; and the activity of viral proteins of neurotropic viruses that target the IFN pathway.
Neurons produce type I interferon during viral encephalitis
TLDR
The data show that, in vivo, neurons take an active part to the antiviral defense by being both IFN-α/β producers and responders.
Type I interferon in neurological disease-the devil from within.
Systemic interferon-α regulates interferon-stimulated genes in the central nervous system
TLDR
Results indicate a direct, STAT1-dependent action of systemic IFN-α in the CNS, which may provide the basis for a mechanism in humans for neurological/neuropsychiatric illnesses associated with IFn-α therapy.
Systemic interferon-alpha regulates interferon-stimulated genes in the central nervous system.
TLDR
Results indicate a direct, STAT1-dependent action of systemic IFN-alpha in the CNS, which may provide the basis for a mechanism in humans for neurological/neuropsychiatric illnesses associated with IFn-alpha therapy.
Differential activation of astrocytes by innate and adaptive immune stimuli
TLDR
It is shown that innate signals LPS– and poly I:C lead to stronger upregulation of TLRs and production of the cytokines IL‐6 and TNF‐α as well as innate immune effector molecules IFN‐α4,IFN‐β, and iNOS compared with cytokine‐stimulated astrocytes.
The interferons and their receptors—distribution and regulation
TLDR
The receptor system utilized by the type I IFNs is discussed and compared with that of the type II and III IFNs, which also regulate immune responses through controlling receptor level on the cell surface.
TYPE I INTERFERONS (/) IN IMMUNITY AND AUTOIMMUNITY
TLDR
The role of IFN-α/β in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases.
Multiple sclerosis: Involvement of interferons in lesion pathogenesis
TLDR
Findings indicate that IFN'γ may play a role in active lesion growth in multiple sclerosis, whereas IFN‐α and IFN•β may exert some local immunosuppressive effect.
...
...