Nucleic acid sensors and type I interferon production in systemic lupus erythematosus

Meena Shrivastav, Timothy B. Niewold

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

Abstract

The characteristic serologic feature of systemic lupus erythematosus (SLE) is autoantibodies against one's own nucleic acid or nucleic acid-binding proteins - DNA and RNA-binding nuclear proteins. Circulating autoantibodies can deposit in the tissue, causing inflammation and production of cytokines such as type 1 interferon (IFN). Investigations in human patients and animal models have implicated environmental as well as genetic factors in the biology of the SLE autoimmune response. Viral/Bacterial nucleic acid is a potent stimulant of innate immunity by both toll-like receptor (TLR) and non-TLR signaling cascades. Additionally, foreign DNA may act as an immunogen to drive an antigen-specific antibody response. Self nucleic acid is normally restricted to the nucleus or the mitochondria, away from the DNA/RNA sensors, and mechanisms exist to differentiate between foreign and self nucleic acid. In normal immunity, a diverse range of DNA and RNA sensors in different cell types form a dynamic and integrated molecular network to prevent viral infection. In SLE, pathologic activation of these sensors occurs via immune complexes consisting of autoantibodies bound to DNA or to nucleic acid-protein complexes. In this review, we will discuss recent studies outlining how mismanaged nucleic acid sensing networks promote autoimmunity and result in the over-production of type I IFN. This information is critical for improving therapeutic strategies for SLE disease.

Original languageEnglish (US)
Article numberArticle 319
JournalFrontiers in immunology
Volume4
Issue numberOCT
DOIs
StatePublished - 2013

Keywords

  • DNA
  • Nucleic acid sensor
  • RNA
  • Systemic lupus erythematosus
  • TLR
  • Type 1 interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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