Human mast cells capture, store, and release bioactive, exogenous IL-17A

J Leukoc Biol. 2016 Sep;100(3):453-62. doi: 10.1189/jlb.3HI1215-542R. Epub 2016 Mar 31.

Abstract

IL-17A, a major proinflammatory cytokine, can be produced by a variety of leukocytes, but its exact cellular source in human inflammatory diseases remains incompletely understood. IL-17A protein is abundantly found in mast cells in human tissues, such as inflamed synovium, but surprisingly, mechanistic murine studies failed to demonstrate IL-17A production by mast cells. Here, we demonstrate that primary human tissue mast cells do not produce IL-17A themselves but actively capture exogenous IL-17A through receptor-mediated endocytosis. The exogenous IL-17A is stored in intracellular granules and can subsequently be released in a bioactive form. This novel mechanism confers to mast cells the capacity to steer IL-17A-mediated tissue inflammation by the rapid release of preformed cytokine.

Keywords: mRNA expression; spondyloarthritis; uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Endocytosis / physiology*
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Mast Cells / cytology
  • Mast Cells / metabolism*
  • Palatine Tonsil / cytology
  • Palatine Tonsil / metabolism*
  • Synoviocytes / cytology
  • Synoviocytes / metabolism*

Substances

  • IL17A protein, human
  • Interleukin-17