The role of interleukin 17 in Crohn’s disease-associated intestinal fibrosis
1 Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
2 Department of Internal Medicine, S. Matteo Hospital, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, University of Pavia, Pavia, Italy
3 Division of Infection, Inflammation and Immunity, University of Southampton, Southampton, UK
4 Surgery Division, Department of Clinical Sciences, L. Sacco University Hospital, Milan, Italy
5 Gastrointestinal Unit, Department of Clinical Sciences, L. Sacco University Hospital, Milan, Italy
6 Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
7 Blizard Institute, Barts and The London School of Medicine and Dentistry, E1 2AT London, UK
Fibrogenesis & Tissue Repair 2013, 6:13 doi:10.1186/1755-1536-6-13Published: 8 July 2013
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.
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.
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.