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

T Noordenbos, I Blijdorp, SJ Chen, J Stap, E Mul, JD Canete, Erik Lubberts, N Yeremenko, D Baeten

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Abstract

Mast cells cannot produce, but take up exogenous IL-17A. 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.
Original languageUndefined/Unknown
Pages (from-to)453-462
Number of pages10
JournalJournal of Leukocyte Biology
Volume100
Issue number3
DOIs
Publication statusPublished - 2016

Research programs

  • EMC MUSC-01-31-01

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