miRNA-451a Targets IFN Regulatory Factor 8 for the Progression of Systemic Lupus Erythematosus

Inflammation. 2017 Apr;40(2):676-687. doi: 10.1007/s10753-017-0514-8.

Abstract

Increasing evidence has shown that miRNA-451a (miR-451a) is associated with the development of systemic lupus erythematosus (SLE); however, the mechanism of this association is not fully known. The present study found an increased expression of miR-451a in the spleen and thymus of an SLE mice model. A decrease in miR-451a expression partly relieved the enlargement of the spleen and decreased the proteinuria content and immune complex deposits. The deficiency in miR-451a also decreased numbers of CD4+CD69+ and CD4+/CD8+ T cells and the levels of the serum cytokines IL-17a and IL-4. The IFN regulatory factor (IRF) 8 was highly expressed in the immune organs of wild-type mice but was suppressed in SLE-like mice. A dual-luciferase reporter assay was carried out in combination with gene silencing and overexpression to verify that IRF8 was a target of miR-451a in vitro and in vivo. The data indicate the function and a target of miR-451a in SLE, providing a new target for SLE therapy.

Keywords: IFN regulatory factor 8; cytokines; immune complex deposit; miRNA-451a; systemic lupus erythematosus.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cytokines / metabolism
  • Disease Progression
  • Gene Expression Regulation / immunology
  • Interferon Regulatory Factors / analysis*
  • Interferon Regulatory Factors / physiology
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / pathology
  • Mice
  • MicroRNAs / analysis*
  • MicroRNAs / physiology
  • Spleen / immunology
  • Spleen / metabolism
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Antigens, CD
  • Cytokines
  • Interferon Regulatory Factors
  • MicroRNAs
  • Mirn451 microRNA, mouse
  • interferon regulatory factor-8