Interleukin‐17A+ Cell Counts Are Increased in Systemic Sclerosis Skin and Their Number Is Inversely Correlated With the Extent of Skin Involvement. Issue 5 (23rd April 2013)

• Record Type: Journal Article
• Authors: Truchetet, Marie‐Elise; Brembilla, Nicolò‐Costantino; Montanari, Elisa; Lonati, Paola; Raschi, Elena; Zeni, Silvana; Fontao, Lionel; Meroni, Pier‐Luigi; Chizzolini, Carlo
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 5(2013:May)
• Page Start: 1347
• Page End: 1356
• Publication Date: 2013-04-23
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37860
• Languages: English
• ISSNs: 0004-3591

Abstract

Abstract: 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.