Elsevier

Autoimmunity Reviews

Volume 12, Issue 5, March 2013, Pages 558-566
Autoimmunity Reviews

Review
Type I interferons in Sjögren's syndrome

https://doi.org/10.1016/j.autrev.2012.10.006Get rights and content
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open access

Abstract

Sjögren's syndrome is a chronic autoimmune disease characterized by lymphocytic infiltration of the salivary and lachrymal glands resulting in dry eyes and mouth. Genetic predisposition, pathogenic infections and hormones have been implicated in the pathogenesis of the disease. Studies in the last several years have revealed marked over-expression of the type I interferon (IFN)-inducible genes in the peripheral blood and salivary glands of patients with Sjögren's syndrome. The expression of the type I IFN-inducible genes in Sjögren's syndrome also positively correlates to titers of anti-Ro and anti-La autoantibodies, which are typical for this disease. Plasmacytoid dendritic cells (pDC) are the major source of type I IFN production and activated pDC are detected in minor salivary gland biopsies from patients with primary Sjögren's syndrome. In addition, polymorphisms in genes important both for the production and response to type I IFN are associated to increased risk for Sjögren's syndrome. Because type I IFN bears a variety of biological functions, such as defense against viral infections and activation of the immune system, these results suggest that the type I IFN system has an important role in the pathogenesis of Sjögren's syndrome. A variety of mechanisms causing an activation of the type I IFN system are discussed in this review. Given the pivotal role of type I IFN in the disease process, therapeutic interventions targeting the type I IFN signaling pathway have the potential to benefit the patients with elevated type I IFN status and such hypothesis needs to be carefully evaluated in clinical development.

Abbreviations

type I IFN
type I interferons
pSjS
primary Sjögren's Syndrome
SLE
systemic lupus erythematosus
pDC
plasmacytoid dendritic cell
iDC
interdigitating dendritic cells
fDC
follicular dendritic cells
NK
natural killer cells
Treg
regulatory T cells
MSG
minor salivary gland
SGEC
salivary gland epithelial cell
PBMC
peripheral blood mononuclear cells
AGS
Aicardi–Goutieres Syndrome

Keywords

Type I interferon
Sjögren's syndrome
Autoimmune
Plasmacytoid dendritic cell
Microarray

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