Tumour necrosis factor superfamily members in the pathogenesis of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the gastrointestinal tract of unclear aetiology of which two major forms are Crohn's disease (CD) and ulcerative colitis (UC). CD and UC are immunologically distinct, although they both result from hyperactivation of proinflammatory pathways in intestines and disruption of intestinal epithelial barrier. Members of the tumour necrosis factor superfamily (TNFSF) are molecules of broad spectrum of activity, including direct disruption of intestinal epithelial barrier integrity and costimulation of proinflammatory functions of lymphocytes. Tumour necrosis factor (TNF) has a well-established pathological role in IBD which also serves as a target in IBD treatment. In this review we discuss the role of TNF and other TNFSF members, notably, TL1A, FasL, LIGHT, TRAIL, and TWEAK, in the pathogenesis of IBD.

Figure 1

Two major mechanisms which implicate the molecules belonging to the TNFSF in the pathomechanisms of IBD. (a) Disruption of intestinal epithelium integrity allows luminal bacterial antigens to cross the epithelial barrier and migrate into the intestinal mucosa where they elicit immune responses. (b) Activation of mucosa-infiltrating T lymphocytes.