Seminars in Immunopathology

, Volume 37, Issue 4, pp 349–357 | Cite as

Type I interferonopathies—an expanding disease spectrum of immunodysregulation

  • Min Ae Lee-Kirsch
  • Christine Wolf
  • Stefanie Kretschmer
  • Axel Roers
Review
First Online:
Received:
Accepted:

Abstract

Type I interferons (IFNs) play a central role in the immune defense against viral infections. Type I IFN signaling is activated by pattern recognition receptors upon sensing of viral nucleic acids and induces antiviral programs through modulation of innate and adaptive immune responses. Type I interferonopathies comprise a heterogenous group of genetically determined diseases that are characterized by inappropriate activation of type I IFN. While their phenotypic spectrum is broad, ranging from severe neurological impairment to mild cutaneous disease, systemic autoinflammation, and autoimmunity are commonly shared signs of type I interferonopathies. Although the mechanisms underlying various disease phenotypes associated with inappropriate type I IFN activation have yet to be fully elucidated, our current understanding of the molecular pathogenesis of type I interferonopathies has provided a set of candidate molecules that can be interrogated in search of targeted therapies.

Keywords

Type I interferonopathies Type I interferon Autoinflammation Autoimmunity Aicardi-Goutières syndrome Familial chilblain lupus Systemic lupus erythematosus 

Abbreviations

ADAR

Adenosine deaminase, RNA-specific

AGS

Aicardi-Goutières syndrome

CANDLE

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome

cGAMP

Cyclic GMP-AMP

cGAS

Cyclic GMP-AMP synthase

IFIH1

Interferon induced with helicase C domain 1

IFN

Interferon

IRF

Interferon-regulatory factor

ISG

Interferon-stimulated gene

MAVS

Mitochondrial antiviral signaling protein

MDA5

Melanoma differentiation-associated gene 5

MYD88

Myeloid differentiation primary-response protein 88

NF-κB

Nuclear factor-κB

RIG-I

Retinoic acid-inducible gene 1

RNASEH2

Ribonuclease H2

RVCL

Retinal vasculopathy with cerebral leukodystrophy

SAMHD1

SAM domain and HD domain-containing protein 1

SAVI

STING-associated vasculopathy, infantile-onset

SLE

Systemic lupus erythematosus

STING

Stimulator of interferon genes

TBK1

TANK-binding kinase 1

TLR

Toll-like receptor

TREX1

3′ Repair exonuclease 1

TRIF

TIR domain-containing adaptor protein inducing IFN-β

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Notes

Acknowledgments

This work was supported by grants from the Deutsche Forschungsgemeinsschaft (Clinical Research Group 249 to M.L.-K. and A.R.) and the Friede Springer Stiftung to M.L.-K.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Min Ae Lee-Kirsch
    • 1
  • Christine Wolf
    • 1
  • Stefanie Kretschmer
    • 1
  • Axel Roers
    • 2
  1. 1.Department of Pediatrics, Medizinische Fakultät Carl Gustav CarusTechnische Universität DresdenDresdenGermany
  2. 2.Institute for Immunology, Medizinische Fakultät Carl Gustav CarusTechnische Universität DresdenDresdenGermany

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