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- Title
Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content.
- Authors
Chen, Sijia; Noordenbos, Troy; Blijdorp, Iris; Mens, Leonieke van; Ambarus, Carmen A; Vogels, Esther; Velde, Anje te; Alsina, Mercé; Cañete, Juan D; Yeremenko, Nataliya; Baeten, Dominique
- 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.
- Subjects
THERAPEUTIC use of monoclonal antibodies; ANKYLOSING spondylitis; CELLULAR signal transduction; DERMIS; IMMUNOHISTOCHEMISTRY; INFLAMMATION; INFLAMMATORY bowel diseases; INTERLEUKINS; MAST cells; MUCOUS membranes; SYNOVIAL membranes; GENE expression profiling
- Publication
Rheumatology, 2019, Vol 58, Issue 4, p617
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/key331