P036. Involvement of gut macrophages in the fibrogenic process in Crohn's disease
P. Biancheri1, A. Di Sabatino1, I. Joe-Njoku2, S.A. Snoek2, C. Salvatore1, P. Giuffrida1, A. Ghanbari2, T.T. MacDonald2, G.R. Corazza1
1Fondazione IRCCS Policlinico S. Matteo, University of Pavia, First Department of Medicine, Italy; 2Blizard Institute, Barts And The London School Of Medicine And Dentistry, Centre for Immunology and Infectious Disease, London, United Kingdom
Background: Intestinal fibrosis and stricture formation are a frequent complication of Crohn's disease (CD). Cytokine driven excessive extracellular matrix deposition and an imbalance between matrix metalloproteinases (MMPs) and their inhibitors are thought to play an important role in the transmural process of stricture development. We have therefore investigated the immunological changes occurring in the deeper layers of the bowel wall in CD patients and control subjects.
Methods: Surgical specimens were collected from strictured and non-strictured ileum of 10 CD patients and from normal ileum of 10 control subjects. The mucosa was removed and discarded. Immunohistochemistry on muscle layers was performed using anti-CD3, ‑CD4, ‑CD8, ‑HLA-DR, and ‑CD68 antibodies. Explants of strictured, non-strictured CD and control gut were cultured ex vivo for 24 h. MMP‑3 expression and collagen, interleukin (IL)-1beta, IL‑6 and tumor necrosis factor (TNF)-alpha levels were measured in organ culture supernatants.
Results: HLA-DR+ cells and macrophages (CD68+ cells) were significantly increased in intestinal CD strictures as compared to non-strictured CD and control gut. No significant differences were found in total T (CD3+), CD4+, and CD8+ cell frequency among the three groups of patients, and in general T cells were infrequent. Collagen and IL‑1beta were significantly increased in organ culture supernatants from strictured CD as compared to those from non-strictured CD and control gut. IL‑6, TNF-alpha and MMP‑3 expression did not differ between strictured, non-strictured CD and control gut supernatants.
Conclusions: The increased frequency of CD68+ cells in CD strictures and the high levels of IL‑1beta in strictured CD supernatants suggest that macrophages may play an important role in driving the processes of fibrogenesis in CD.