title: The role of interleukin 17 in Crohn's disease-associated intestinal fibrosis.
abstract: BACKGROUND
  Interleukin (IL)-17A and IL-17E (also known as IL-25) have been implicated in fibrosis in various tissues. However, the role of these cytokines in the development of intestinal strictures in Crohn's disease (CD) has not been explored. We investigated the levels of IL-17A and IL-17E and their receptors in CD strictured and non-strictured gut, and the effects of IL-17A and IL-17E on CD myofibroblasts.
  
  
  RESULTS
  IL-17A was significantly overexpressed in strictured compared with non-strictured CD tissues, whereas no significant difference was found in the expression of IL-17E or IL-17A and IL-17E receptors (IL-17RC and IL-17RB, respectively) in strictured and non-strictured CD areas. Strictured CD explants released significantly higher amounts of IL-17A than non-strictured explants, whereas no difference was found as for IL-17E, IL-6, or tumor necrosis factor-α production. IL-17A, but not IL-17E, significantly inhibited myofibroblast migration, and also significantly upregulated matrix metalloproteinase (MMP)-3, MMP-12, tissue inhibitor of metalloproteinase-1 and collagen production by myofibroblasts from strictured CD tissues.
  
  
  CONCLUSIONS
  Our results suggest that IL-17A, but not IL-17E, is pro-fibrotic in CD. Further studies are needed to clarify whether the therapeutic blockade of IL-17A through the anti-IL-17A monoclonal antibody secukinumab is able to counteract the fibrogenic process in CD.
authors.affiliation: Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK. t.t.macdonald@qmul.ac.uk.
authors.forename: Paolo
authors.initials: P
authors.lastname: Biancheri
authors.forename: Sylvia Lf
authors.initials: SL
authors.lastname: Pender
authors.forename: Francesca
authors.initials: F
authors.lastname: Ammoscato
authors.forename: Paolo
authors.initials: P
authors.lastname: Giuffrida
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sampietro
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
authors.forename: Amir
authors.initials: A
authors.lastname: Ghanbari
authors.forename: Renata
authors.initials: R
authors.lastname: Curciarello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pasini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
authors.forename: Gino R
authors.initials: GR
authors.lastname: Corazza
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Macdonald
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino