IL-17A is a novel player in dialysis-induced peritoneal damage

Kidney Int. 2014 Aug;86(2):303-15. doi: 10.1038/ki.2014.33. Epub 2014 Feb 19.

Abstract

The classical view of the immune system has changed by the discovery of novel T-helper (Th) subsets, including Th17 (IL-17A-producing cells). IL-17A participates in immune-mediated glomerulonephritis and more recently in inflammatory pathologies, including experimental renal injury. Peritoneal dialysis patients present chronic inflammation and Th1/Th2 imbalance, but the role of the Th17 response in peritoneal membrane damage has not been investigated. In peritoneal biopsies from dialyzed patients, IL-17A immunostaining was found mainly in inflammatory areas and was absent in the healthy peritoneum. IL-17A-expressing cells included lymphocytes (CD4+ and γδ), neutrophils, and mast cells. Elevated IL-17A effluent concentrations were found in long-term peritoneal dialysis patients. Studies in mice showed that repeated exposure to recombinant IL-17A caused peritoneal inflammation and fibrosis. Moreover, chronic exposure to dialysis fluids resulted in a peritoneal Th17 response, including elevated IL-17A gene and protein production, submesothelial cell infiltration of IL-17A-expressing cells, and upregulation of Th17 differentiation factors and cytokines. IL-17A neutralization diminished experimental peritoneal inflammation and fibrosis caused by chronic exposure to dialysis fluids in mice. Thus, IL-17A is a key player of peritoneum damage and it may be a good candidate for therapeutic intervention in peritoneal dialysis patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Cytokines / metabolism
  • Dialysis Solutions / adverse effects
  • Female
  • Humans
  • Interleukin-17 / administration & dosage
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Peritoneal Dialysis / adverse effects*
  • Peritoneum / immunology*
  • Peritoneum / injuries*
  • Peritoneum / pathology
  • Peritonitis / etiology
  • Peritonitis / immunology
  • Peritonitis / pathology
  • Th17 Cells / immunology
  • Transcription Factors / metabolism

Substances

  • Antibodies, Neutralizing
  • Cytokines
  • Dialysis Solutions
  • IL17A protein, human
  • Interleukin-17
  • Transcription Factors