Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice

Sci Rep. 2021 Aug 11;11(1):16348. doi: 10.1038/s41598-021-94855-5.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies
  • Cathepsins / metabolism*
  • Female
  • Humans
  • Interferon-alpha / metabolism*
  • Lupus Erythematosus, Systemic / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Monocytes / metabolism
  • Neutrophils / metabolism
  • Toll-Like Receptor 7 / metabolism*
  • Up-Regulation / physiology*

Substances

  • Autoantibodies
  • Interferon-alpha
  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Cathepsins
  • cathepsin S