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.
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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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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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This article is a contribution to the Special Issue on The Inflammasome and Autoinflammatory Diseases - Guest Editors: Seth L. Masters, Tilmann Kallinich and Seza Ozen
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Lee-Kirsch, M.A., Wolf, C., Kretschmer, S. et al. Type I interferonopathies—an expanding disease spectrum of immunodysregulation. Semin Immunopathol 37, 349–357 (2015). https://doi.org/10.1007/s00281-015-0500-x
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DOI: https://doi.org/10.1007/s00281-015-0500-x