title: Defects in mucosal immunity leading to ulcerative colitis.
abstract: Evidence accumulated over the last decade demonstrates that what we call 'ulcerative colitis' is actually a heterogeneous group of diseases resulting from different pathogenic mechanisms with a common symptomatic expression. Subgroups of patients with ulcerative colitis can be stratified by presence or absence of serum autoantibodies, which are thought not to be pathogenic but to mark for a distinct disease phenotype. In recent years, animal-based experimental systems have emerged that reflect human ulcerative colitis and have potential to accelerate our understanding of its pathogenesis. Genetic and immunological data from human studies in combination with results from animal model systems are the foundation of a hypothesis, which includes a role for microbial antigen exposure in the initiation, perpetuation, and amplification of the disease. In ulcerative colitis, it appears as though the T-cell response to the antigens is not T-helper (Th) 1 dominant as in the case of Crohn's disease but rather is either Th2 [interleukin (IL)-4, IL-13] or is mediated by specialized cells such as natural killer (NK) T cells (IL-13). Lamina propria T cells from ulcerative colitis patients produce significantly greater amounts of IL-13. Ulcerative colitis is associated with an atypical Th2 response mediated by a distinct subset of NK T cells that produce IL-13 and are cytotoxic for epithelial cells. The way in which this response affects the ultimate cascade of inflammatory events has yet to be determined.
authors.affiliation: Division of Gastroenterology, Inflammatory Bowel Disease Center, Immunobiology Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. targans@cshs.org
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Loren C
authors.initials: LC
authors.lastname: Karp
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology*