OBJECTIVE: Levels of interleukin-17A (IL-17A) have been found to be increased in synovial fluid from individuals with systemic sclerosis (SSc). This study was undertaken to investigate whether IL-17A-producing cells are present in affected SSc skin, and whether IL-17A exerts a role in the transdifferentiation of myofibroblasts. METHODS: Skin biopsy samples were obtained from the involved skin of 8 SSc patients and from 8 healthy control donors undergoing plastic surgery. Immunohistochemistry and multicolor immunofluorescence techniques were used to identify and quantify the cell subsets in vivo, including IL-17A+, IL-4+, CD3+, tryptase-positive, α-smooth muscle actin (α-SMA)-positive, myeloperoxidase-positive, and CD1a+ cells. Dermal fibroblast cell lines were generated from all skin biopsy samples, and quantitative polymerase chain reaction, Western blotting, and solid-phase assays were used to quantify α-SMA, type I collagen, and matrix metalloproteinase 1 (MMP-1) production by the cultured fibroblasts. RESULTS: IL-17A+ cells were significantly more numerous in SSc skin than in healthy control skin (P = 0.0019) and were observed to be present in both the superficial and deep dermis. Involvement of both T cells and tryptase-positive mast cells in the production of IL-17A was observed. Fibroblasts positive for α-SMA were found adjacent to IL-17A+ cells, but not IL-4+ cells. However, IL-17A did not induce α-SMA expression in cultured fibroblasts. In the presence of IL-17A, the α-SMA expression induced in response to transforming growth factor β was decreased, while MMP-1 production was directly enhanced. Furthermore, the frequency of IL-17A+ cells was higher in the skin of SSc patients with greater severity of skin fibrosis (lower global skin thickness score). CONCLUSION: IL-17A+ cells belonging to the innate and adaptive immune system are numerous in SSc skin. IL-17A participates in inflammation while exerting an inhibitory activity on myofibroblast transdifferentiation. These findings are consistent with the notion that IL-17A has a direct negative-regulatory role in the development of dermal fibrosis in humans.
Interleukin-17A+ cell counts are increased in systemic sclerosis skin and their number is inversely correlated with the extent of skin involvement / M. Truchetet, N. Brembilla, E. Montanari, P. Lonati, E. Raschi, S. Zeni, L. Fontao, P. Meroni, C. Chizzolini. - In: ARTHRITIS AND RHEUMATISM. - ISSN 0004-3591. - 65:5(2013 May), pp. 1347-1356.
|Titolo:||Interleukin-17A+ cell counts are increased in systemic sclerosis skin and their number is inversely correlated with the extent of skin involvement|
|Parole Chiave:||Adaptive Immunity ; Adult ; Aged ; Biological Markers ; Cell Count ; Cell Transdifferentiation ; Dermis ; Female ; Humans ; Immunity, Innate ; Interleukin-17 ; Male ; Middle Aged ; Myofibroblasts ; Scleroderma, Systemic|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||mag-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/art.37860|
|Appare nelle tipologie:||01 - Articolo su periodico|