title: Interleukin-17A+ cell counts are increased in systemic sclerosis skin and their number is inversely correlated with the extent of skin involvement.
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).
  
  
  CONCLUSIONS
  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.
authors: Geneva University Hospital, Geneva, Switzerland.
authors: Marie-Elise
authors: ME
authors: Truchetet
authors: Nicolò-Costantino
authors: NC
authors: Brembilla
authors: Elisa
authors: E
authors: Montanari
authors: Paola
authors: P
authors: Lonati
authors: Elena
authors: E
authors: Raschi
authors: Silvana
authors: S
authors: Zeni
authors: Lionel
authors: L
authors: Fontao
authors: Pier-Luigi
authors: PL
authors: Meroni
authors: Carlo
authors: C
authors: Chizzolini
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D054338:Cell Transdifferentiation; D020405:Dermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D012595:Scleroderma, Systemic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; C508717:IL17A protein, human; D020381:Interleukin-17