Article Text

Download PDFPDF
Immunopathogenesis of IBD: insufficient suppressor function in the gut?
  1. I L Huibregtse1,
  2. A U van Lent2,
  3. S J H van Deventer1
  1. 1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to:
    Dr S J H van Deventer
    Academic Medical Center/University of Amsterdam, Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; s.j.vandeventer{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


The intestinal immune system is in a constant state of controlled inflammation, and there is substantial evidence that loss of control is an important pathogenic mechanism in inflammatory bowel diseases (IBD). A major current working hypothesis defines Crohn’s disease as a dysregulated immune response towards components of the intestinal flora, leading to chronic intestinal inflammation.1 The causes for this inappropriate response can be attributed to (a combination of) defects in the epithelial barrier, the innate immune response or the adaptive immune response.

Animal experiments as well as clinical data indicate that the immunopathogenesis of Crohn’s disease and ulcerative colitis differ at the level of T cell differentiation and activation although the governing mechanisms responsible for these differences have been incompletely defined. In both diseases, activation of T cells is evident but pathogenic T cells in Crohn’s disease predominantly produce interferon γ (membrane bound), tumour necrosis factor (TNF)α and interleukin (IL)-23 whereas ulcerative colitis is characterised by production of IL-5 and IL-13.2,3

The increased production of “Th1” type cytokines in Crohn’s disease is probably related to increased activation of mucosal dendritic cells and macrophages, and the pivotal function of membrane associated (Toll-like receptor (TLR)) and intracellular (nucleotide oligomerisation domain (NOD) family) receptors in the activation of these antigen presenting cells (APC) has now been well established. Both receptors are key mediators of innate host defence, crucially involved in maintaining intestinal homeostasis.4 In healthy subjects, the colonic mucosa harbours “non-inflammatory” dendritic cells, expressing low levels of TLR2 and TLR4 and producing cytokines such as IL-10, contributing to a non-inflammatory environment,5,6 but in the mucosa of patients with Crohn’s disease the production of IL-12 is greatly increased.7–,9 Dendritic cells in both ulcerative colitis and Crohn’s disease have an activated phenotype with higher levels of …

View Full Text


  • Competing interests: None.