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;
Core Facility Cellular Imaging/van Leeuwenhoek Centre for Advanced Microscopy-Academisch Medisch Centrum, Academic Medical Center/University of Amsterdam, The Netherlands;
J Leukoc Biol. 2016 Sep;100(3):453-62. doi: 10.1189/jlb.3HI1215-542R. Epub 2016 Mar 31.
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.
IL-17A 是一种主要的促炎细胞因子，可由多种白细胞产生，但在人类炎症性疾病中其确切的细胞来源尚不完全清楚。IL-17A 蛋白在人类组织中的肥大细胞中大量存在，如发炎的滑膜，但令人惊讶的是，机制性的鼠类研究未能证明肥大细胞产生 IL-17A。在这里，我们证明原代人组织肥大细胞本身并不产生 IL-17A，而是通过受体介导的内吞作用主动捕获外源性的 IL-17A。外源性的 IL-17A 储存在细胞内颗粒中，随后可以以生物活性形式释放。这种新的机制赋予肥大细胞通过快速释放预先形成的细胞因子来控制由 IL-17A 介导的组织炎症的能力。
