Reduced RING finger protein 10 expression in macrophages is associated with aging-related inflammation

FEBS Open Bio. 2021 Feb;11(2):386-394. doi: 10.1002/2211-5463.13049. Epub 2021 Jan 13.

Abstract

Age-associated decline of the immune system is referred to as immunosenescence. The E3 ligase RING finger 10 (RNF10) has long been associated with the innate immune response, although a potential role in immunosenescence has not previously been reported. In the present study, we identified that RNF10 expression is lower in aged mouse macrophages than in young cells. After lipopolysaccharide stimulation, RNF10 expression remained at a basal low level in aged mouse cells, but declined sharply in young mouse cells. Knockdown of RNF10 enhanced both the nuclear factor-κB and interferon regulatory factor 3 signaling pathways and thus enhanced proinflammatory cytokines and type I interferons in macrophages, promoting clearance of Listeria monocytogenes. These findings indicate that dysregulated expression of RNF10 is associated with age-associated immune dysfunction, and RNF10 may thus be a potential target for the treatment of age-related inflammatory diseases.

Keywords: E3 ubiquitin ligase; RNF10; immunosenescence; inflammation; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / blood
  • Aging / immunology*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Humans
  • Inflammation / immunology
  • Interferon Type I / metabolism
  • Lipopolysaccharides / immunology
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology*
  • Listeriosis / microbiology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mice

Substances

  • Carrier Proteins
  • Interferon Type I
  • Lipopolysaccharides
  • Rnf10 protein, mouse