Interleukin-17A+ Cell Counts Are Increased in Systemic Sclerosis Skin and Their Number Is Inversely Correlated With the Extent of Skin Involvement
Version of Record online: 23 APR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 5, pages 1347–1356, May 2013
How to Cite
Truchetet, M.-E., Brembilla, N.-C., Montanari, E., Lonati, P., Raschi, E., Zeni, S., Fontao, L., Meroni, P.-L. and Chizzolini, C. (2013), Interleukin-17A+ Cell Counts Are Increased in Systemic Sclerosis Skin and Their Number Is Inversely Correlated With the Extent of Skin Involvement. Arthritis & Rheumatism, 65: 1347–1356. doi: 10.1002/art.37860
- Issue online: 23 APR 2013
- Version of Record online: 23 APR 2013
- Accepted manuscript online: 17 JAN 2013 03:39PM EST
- Manuscript Accepted: 3 JAN 2013
- Manuscript Received: 15 AUG 2012
- Swiss National Science Foundation. Grant Numbers: 31003A_124941/1, 310030_140791
- Association des Sclérodermiques de France
- Société Française de Rhumatologie, France
- Manodori Foundation, Reggio Emilia, Italy
- IRCCS Istituto Auxologico Italiano, Italy
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.
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.
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).
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.