Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content

• Published in: Rheumatology (Oxford, England) England), 2019-04, Vol.58 (4), p.617-627
• Main Authors: Chen, Sijia, Noordenbos, Troy, Blijdorp, Iris, van Mens, Leonieke, Ambarus, Carmen A, Vogels, Esther, te Velde, Anje, Alsina, Mercé, Cañete, Juan D, Yeremenko, Nataliya, Baeten, Dominique
• Format: Article
• Language: English
• Subjects: Allergic diseases; Arthritis; Cell activation; Cell Culture Techniques; Dermis; Gene expression; Histamine; Humans; Immunohistochemistry; Inflammation; Inflammatory bowel diseases; Inflammatory diseases; Interleukin-17 - metabolism; Intestine; Lamina propria; Mast cells; Mast Cells - metabolism; Monoclonal antibodies; Rheumatic diseases; Signal transduction; Spondylarthritis - metabolism; Synoviocytes - metabolism
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/key331

Abstract Objectives Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA. Methods Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions. Results IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria. Conclusion IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.