Absence of a role for interleukin‐13 in inflammatory bowel disease

Abstract

IL-13 has been implicated in the pathogenesis of ulcerative colitis (UC), and may have a role in animal models of gut fibrosis. We studied the involvement of IL-13 in inflammation and fibrosis in UC and Crohn's disease (CD). Intestinal biopsies and anti-CD3/CD28-or anti-CD2/CD28-stimulated lamina propria mononuclear cells from UC and CD patients and control subjects were cultured, and IL-13, IL-4, IL-5, IL-17A and IFN-γ production was measured. Mucosal IL-13-producing cells were characterised by flow cytometry. Gut explants from strictured CD, non-strictured CD and healthy donors were cultured ex vivo, and secreted IL-13, IL-1β and collagen were measured. IL-13 production by mucosal explants and activated lamina propria mononuclear cells did not differ between CD, UC and control subjects, and was at least a log lower than IFN-γ and IL-17A. IL-13-producing cells, and in particular natural killer T cells, were uniformly low in all groups. IL-4 and IL-5 were undetectable in culture supernatants. Explants of CD strictures produced low amounts of IL-13, whereas IL-1β and collagen were elevated. We could not confirm that UC or strictured CD are associated with elevated IL-13 production. These data suggest that an anti-IL-13 Ab would not be an appropriate therapeutic strategy in inflammatory bowel disease. Keywords:Crohn's disease r Fibrosis r T helper cell type 2 r Ulcerative colitis Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Prof. Thomas T. MacDonald e-mail: t.t.macdonald@qmul.ac.uk * These authors contributed equally to this manuscript.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 370-385 Cellular immune response 371 IntroductionCrohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel disorders thought to be caused by an abnormal immune response against the normal microbial flora [1]. Until recent years, intestinal lesions in CD were thought to be the end result of a T helper cell type (Th)1 response, with overproduction of . However, more recently, two novel subsets of CD4 + T cells, namely Th17 cells, which produce the proinflammatory cytokine IL-17A, and Th1/Th17 cells, which release both IFN-γ and IL-17A, have been identified [3,4]. IL-17A is overexpressed in both CD and UC mucosa, and an increased number of Th17 and Th1/Th17 cells has been found in the lamina propria of inflammatory bowel disease patients compared with controls, suggesting that, in addition to Th1 cells, Th17 responses may play an important role in the pathogenesis of both CD and UC [5][6][7]. As opposed to CD, mucosal inflammation in UC is thought to be driven by Th2 cytokines, such as IL-5 and IL-13 [2]. IL-13 is a pleiotropic cytokine with effects on many cell types, including macrophages, epithelial cells, smooth muscle cells and neurons [8]. IL-13, produced by Th2 cells and CD1d-restricted natural killer T (NKT) cells, has been implicated in the pathogenesis of an UC-like model of...

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