Type I Interferons in the Pathogenesis and Treatment of Autoimmune Diseases

Abstract

Type I interferons (IFN-Is) are a very important group of cytokines that are produced by innate immune cells but also act on adaptive immune cells. IFN-Is possess antiviral, antitumor, and anti-proliferative effects, as well are associated with the initiation and maintenance of autoimmune disorders. Studies have shown that aberrantly expressed IFN-Is and/or type I IFN-inducible gene signatures in the serum or tissues of patients with autoimmune disorders are linked to their pathogenesis, clinical manifestations, and disease activity. Type I interferonopathies with mutations in genes impacting the type I IFN signaling pathway have shown symptoms and characteristics similar to those of systemic lupus erythematosus (SLE). Furthermore, both interventions in animal models and clinical trials of therapies targeting the type I IFN signaling pathway have shown efficacy in the treatment of autoimmune diseases. Our review aims to summarize the functions and targeted therapies (as well as clinical trials) of IFN-Is in both adult and pediatric autoimmune diseases, such as SLE, pediatric SLE (pSLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), Sjögren syndrome (SjS), and systemic sclerosis (SSc), discussing the potential abnormal regulation of transcription factors and epigenetic modifications and providing a potential mechanism for pathogenesis and therapeutic strategies for future clinical use.

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Abbreviations

AGS:

Aicardi-Goutières syndrome

BTK:

Bruton’s tyrosine kinase

cGAS:

Cyclic GMP-AMP synthase

IFN-I:

Type I interferon

IRAK:

Interleukin-1 receptor-associated kinase

IRF:

Interferon regulatory family

ISG:

Interferon-stimulated gene

JAK:

Janus kinase

JDM:

Juvenile dermatomyositis

JIA:

Juvenile idiopathic arthritis

MAVS:

Mitochondrial antiviral signaling protein

MDA:

Melanoma differentiation-associated gene

MyD:

Myeloid differentiation primary response gene

pDC:

Plasmacytoid dendritic cell

PRR:

Pattern recognition receptor

pSjS:

primary Sjögren syndrome

pSLE:

Pediatric systemic lupus erythematosus

RA:

Rheumatoid arthritis

RIG-I:

Retinoic acid-inducible gene-I

SSc:

Systemic sclerosis

STAT:

Signal transducers and activators of transcription

STING:

Stimulator of interferon

Syk:

Spleen tyrosine kinase

TBK:

TANK-binding kinase

TLR:

Toll-like receptor

TRAF:

Tumor necrosis factor receptor-associated factor

TREX:

Three prime repair exonuclease

TRIF:

Toll-IL-1 receptor domain-containing adaptor inducing IFN-β

TYK:

Tyrosine kinase

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Acknowledgments

We thank Xing Wang, Meixi Liu, Zhenwei Tang, and Bowen Li for their guidance in revising the manuscript.

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Concept and design: Qianjin Lu, Haijing Wu, Ming Zhao, Jiao Jiang; Drafting of the manuscript: Jiao Jiang; Revising of the manuscript: Qianjin Lu, Haijing Wu, Christopher Chang, Ming Zhao, Jiao Jiang.

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This work was supported by the National Natural Science Foundation of China (No. 81972943 and No. 81830097) and the Hunan Talent Young Investigator (No. 2019RS2012).

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Correspondence to Haijing Wu or Qianjin Lu.

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Jiang, J., Zhao, M., Chang, C. et al. Type I Interferons in the Pathogenesis and Treatment of Autoimmune Diseases. Clinic Rev Allerg Immunol 59, 248–272 (2020). https://doi.org/10.1007/s12016-020-08798-2

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Keywords

  • Autoimmune disease
  • Type I interferon signaling pathway
  • Epigenetic modifications
  • Systemic lupus erythematosus
  • Juvenile idiopathic arthritis
  • Sjogren’s syndrome
  • Interferonopathies