title: Human mast cells capture, store, and release bioactive, exogenous IL-17A.
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.
authors.affiliation: Amsterdam Rheumatology and Immunology Center and Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands;
authors.forename: Troy
authors.initials: T
authors.lastname: Noordenbos
authors.affiliation: Amsterdam Rheumatology and Immunology Center and Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands;
authors.forename: Iris
authors.initials: I
authors.lastname: Blijdorp
authors.affiliation: Amsterdam Rheumatology and Immunology Center and Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands;
authors.forename: Sijia
authors.initials: S
authors.lastname: Chen
authors.affiliation: Core Facility Cellular Imaging/van Leeuwenhoek Centre for Advanced Microscopy-Academisch Medisch Centrum, Academic Medical Center/University of Amsterdam, The Netherlands;
authors.forename: Jan
authors.initials: J
authors.lastname: Stap
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Swammerdam Institute for Life Sciences, Academic Medical Center/University of Amsterdam, The Netherlands;
authors.forename: Erik
authors.initials: E
authors.lastname: Mul
authors.affiliation: Hospital Clinic de Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
authors.affiliation: Amsterdam Rheumatology and Immunology Center and Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands;
authors.forename: Nataliya
authors.initials: N
authors.lastname: Yeremenko
authors.affiliation: Amsterdam Rheumatology and Immunology Center and Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, The Netherlands; d.l.baeten@amc.uva.nl.
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology / Q000378:metabolism*; D000070918:Synoviocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17
keywords: mRNA expression; spondyloarthritis; uptake