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Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
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Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by

Sijia Chen1,2, Troy Noordenbos1,2, Iris Blijdorp1,2

  • 1Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.

Rheumatology (Oxford, England)
|December 6, 2018
PubMed
Abstract

Insights

Mast cells in SpA tissues store IL-17A, a key inflammatory driver. These sentinel cells may release IL-17A to amplify inflammation, though their IL-17A content appears regulated by disease state.

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Mast cells in synovial tissue contain Interleukin-17A (IL-17A), a critical mediator of inflammation in Spondyloarthritis (SpA).
  • In vitro studies suggest mast cells can capture and release exogenous IL-17A, raising questions about their role in SpA pathogenesis.

Purpose of the Study:

  • To investigate whether mast cells contribute to SpA tissue inflammation by capturing and releasing IL-17A.
  • To assess the presence and regulation of IL-17A-positive mast cells in SpA target tissues.

Main Methods:

  • Gene expression analysis of the LAD2 mast cell line to assess potential IL-17A activation.
  • Immunohistochemistry to detect IL-17A-positive mast cells in synovial, skin, and gut tissues from SpA patients, before and after secukinumab treatment.

Main Results:

  • IL-17A did not induce a pro-inflammatory response in LAD2 mast cells via the canonical pathway.
  • IL-17A-positive mast cells were found in SpA synovial tissue, skin, and gut, increasing after secukinumab treatment.
  • While increased in psoriatic skin and IBD gut submucosa, IL-17A-positive mast cells were less abundant in inflamed gut lamina propria compared to non-inflamed tissue.

Conclusions:

  • IL-17A-positive mast cells are present in SpA target tissues and their IL-17A content is regulated, inversely correlating with inflammation.
  • Tissue-resident mast cells may function as IL-17A reservoirs, releasing the cytokine to potentially amplify tissue inflammation in SpA.
Keywords:
IL-17Aanti-IL-17A therapy (secukinumab)mast cells

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