Immunopathogenesis of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract. Familial and epidemiological studies have stressed the involvement of genetic factors and have also shown the critical role of environmental factors such as sanitation and hygiene in the development of IBD. However, the molecular mechanisms of intestinal inflammation in IBD have long remained unknown. In recent years, the study of susceptibility genes involved in the detection of bacterial components and in the regulation of the host immune response has shed light onto the potential role of intestinal pathogens and gut flora in IBD immunobiology. This review presents current knowledge on intestinal epithelial barrier alterations and on dysfunction of mucosal innate and acquired immune responses in IBD. The data support the etiological hypothesis which argues that pathogenic intestinal bacteria and/or infectious agents initiate and perpetuate the inflammation of the gut through disruption of tolerance towards the commensal microbiota in an individual with genetic vulnerability.

Figure 1

Most important mechanisms of defence in the intestinal epithelial barrier. Invasion of the mucosa is prevented by physical defences (mucus layer secreted by goblet cells, cellular barrier formed by epithelial cells) and by epithelial immune cells (Paneth cells and M cells). Recognition of pathogenic bacterial components is performed via TLR and NOD receptors. The inflammatory reaction involves mucosal immune system activation (mononuclear cells, lymphocytes and dendritic cells of the subepithelial dome). Inflammation is mediated by cytokines (TNF, IL) secreted by these different immune cells. EGF, epithelial growth factor; GM-CSF, granulocyte macrophage-colony stimulating factor; FAE, follicle-associated epithelium; ITF, intestinal trefoil factor; IL, interleukin; NOD2, nucleotide oligomerization domain 2; SED, subepithelial dome of the Peyer patch; Th, T helper lymphocyte; TLR, toll-like receptor; TNF, tumor necrosis factor. Source: Med Sci (Paris) 2010; 26:405–10.

Figure 2

Differentiation of naive T cells (Th0). CD, cluster of differentiation; Th, T helper lymphocyte; IFNγ, interferon gamma; IL, interleukin; TGFβ, transforming growth factor β. Source: Med Sci (Paris) 2010; 26:405–10.