Session Type: Abstract Submissions (ACR)
Background/Purpose: T cell producing IL-17A are increased in the peripheral blood of individuals affected by systemic sclerosis (SSc). We asked the question whether IL-17A-producing cells are present in affected SSc skin and whether they exert any role in myofibroblasts induction.
Bioptic material was obtained from the involved skin of 8 SSc and 8 healthy donors (HD) undergoing plastic surgery. We adopted an immunohistochemistry and multicolor immunofluorescence approach to identify and quantify in vivo IL-17A+, IL-4+, CD3+, tryptase+, alpha-smooth muscle (aSMA)+, myeloperoxidase+, CD1a+ cells. Dermal fibroblasts cell lines were generated from all biopsies. Quantitative PCR, westernblot, and solid phase assays used to quantify aSMA, and matrix metalloproteinase-1 (MMP1) production by cultured fibroblasts.
Results: IL-17A+ cells were significantly more numerous in SSc than HD skin (p=0.004) and present in both superficial and deep dermis. Most of these cells (>60%) were tryptase+ mast cells and between 10 to 20% Th17 cells. Some IL-17A+, but no IL-4+ cells were found adjacent to aSMA+ fibroblasts. However, IL-17A did not induce aSMA-expression in cultured fibroblasts and decreased aSMA-expression induced by transforming growth factor-beta, while directly enhancing MMP-1 production. Furthermore, the frequency of IL-17A+ cells was higher in the skin of SSc individuals with lower global skin thickness score.
Conclusion: IL-17A+ cells belonging to the innate and adaptive immune system are numerous in SSc skin where IL-17A participates to inflammation and exerts an inhibitory activity on myofibroblast differentiation. These data are consistent with a direct negative regulatory role for IL-17A in the development of dermal fibrosis in humans.
M. E. Truchetet,
N. C. Brembilla,
P. L. Meroni,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-17a-positive-cells-are-increased-in-systemic-sclerosis-skin-and-their-number-is-inversely-correlated-to-skin-thickness/