Review article: the aetiopathogenesis of inflammatory bowel disease--immunology and repair mechanisms.
Although the aetiopathogenesis of Crohn's disease and ulcerative colitis, remains unsolved, current evidence indicates that defective T-cell apoptosis and impairment of intestinal epithelial barrier function play important roles in the pathogenesis of both conditions. Without appropriate control of T-cell proliferation and death during an immune response, an inappropriate accumulation of T cells and subsequent intestinal inflammation may occur. Differences in T-cell responses between Crohn's disease and ulcerative colitis have been identified, with mucosal T-cell apoptosis being defective in Crohn's disease, but not in ulcerative colitis. Furthermore, cell cycling is considerably faster, with a vigorous clonal expansion, in Crohn's disease, whereas, in ulcerative colitis, T cells cycle normally, but have a remarkably reduced capacity to divide and expand. The elimination of excessive T cells therefore seems to be a reasonable approach to restore the gut to a physiological state or, at least, a controlled state of inflammation. The tumour necrosis factor-alpha blocker, infliximab, exerts its beneficial effects, at least in part, by the induction of apoptosis in lamina propria T cells and monocytes. In addition, repeated damage and injury of the intestinal surface is a hallmark of inflammatory bowel disease and may facilitate the entry of luminal antigens into the mammalian organism and the initiation and perpetuation of both nonspecific and specific immune responses. A better understanding of and enhancement of intestinal repair mechanisms may thus provide future approaches for the treatment of inflammatory bowel disease.
Dignass
A U
AU
Department of Medicine, Division of Hepatology and Gastroenterology, Charité Medical School--Virchow Hospital, Berlin, Germany. axel.dignass@charite.de
Baumgart
D C
DC
Sturm
A
A
D041981:Gastrointestinal Tract / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D014945:Wound Healing / Q000276:immunology