Recent Developments in the Immunology of Inflammatory Bowel Disease

Abstract

Crohn's disease and ulcerative colitis are caused by excessive immune reactivity in the gut wall. Analysis of the type of immune responses ongoing in diseased gut has revealed important features which suggest that these conditions are different. In Crohn's disease tissue there is considerable evidence for an ongoing T helper cell type 1 response, with excess interleukin‐12, interferon‐γ and TNF‐α. There is circumstantial evidence in patients that this response is directed against the normal bacterial flora and definitive evidence in mouse models that T cell responses to the flora cause gut disease. In ulcerative colitis, the role of tissue damaging T cell responses in the gut mucosa is much less clear and there is more evidence that the lesion is owing to antibody‐mediated hypersensitivity. Although different types of immune reactions initiate tissue injury in both Crohn's disease and ulcerative colitis, the downstream events which actually damage the tissue are the same in each condition. Elevated cytokine concentrations in the mucosa lead to the production of excess matrix degrading enzymes by gut fibroblasts, loss of mucosal integrity and ulceration. The same process also leads to an increased production of epithelial growth factors such as KGF Keratinocyte Growth Factor by gut fibroblasts and produces the crypt cell hyperplasia characteristic of all gut inflammatory conditions.

Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors

“…Increased FGF7 expression is an important response mechanism to damaged epithelial tissues in the skin, bladder, and kidney (47). Conversely, overexpression of FGF7 is thought to contribute to psoriasis and inflammatory bowel disease (48,49). FGF10͞7-FGFR2b signaling is also involved in the pathogenesis of bladder, colon, and prostate cancers (50)(51)(52).…”

Acute and persisting Th2-like immune response after fractionated colorectal γ-irradiation

“…Many diseases, including inflammatory bowel disease [8] , are associated with imbalances between Th1 (T helper cell type 1) and Th2 (T helper cell type 2) cytokines. Because these cell subpopulations tend to function antagonistically towards each another, the persistence of disease susceptibility and resistance depends on the profiles of the cytokines that each type secretes.…”

The effect of the hookworm Ancylostoma ceylanicum on the mucosal architecture of the small intestine in hamsters

“…fats and vitamins) (MacDonald et al, 1999;Cliffe et al, 2005). Enteropathy can stem from inappropriate immune responses to food antigens and components of the symbiotic intestinal bacterial flora, through components of the host's response to infection, as well as from the direct activities of the infectious organisms, via damage to the mucosa by released toxins or feeding activities (Castro, 1990;Behnke, 1991;Cooper et al, 1992;Garside et al, 2000;MacDonald et al, 2000;Graham et al, 2004).…”