Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content.
Rheumatology (Oxford)
; 58(4): 617-627, 2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30517745
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-17
/
Espondilartrite
/
Sinoviócitos
/
Mastócitos
Limite:
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda