Ulcerative Colitis: Pathogenesis

Author(s): Walter Fries, Salvatore Comunale.

Journal Name: Current Drug Targets

Volume 12 , Issue 10 , 2011

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Abstract:

The pathogenesis of ulcerative is still poorly understood. With the introduction of new culture-independent techniques the research on the intestinal microbiota has revealed an important reduction of Bacteroidetes and Firmicutes leading to a reduced biodiversity and dysbiosis in these patients. Going in depth, the intestinal barrier is covered under physiologic conditions by a mostly sterile mucus layer. Besides a reduction of mucus thickness or an alteration in mucus composition hypothesized for human ulcerative colitis, new evidence coming from mouse models has introduced a novel concept based on cellular stress due to misfolded mucus-associated proteins opening a new research area for the epithelial cell lining. A dysregulated immune response involving the innate (e.g. toll-like receptors, dendritic cells, etc) and the adaptive immune system (e.g. effector T-cells, regulatory T-cells, eosinophils, neutrophils, etc) may follow or precede the macroscopic lesions. The immune response in ulcerative colitis is represented principally by secretion of interleukin-5 and -13 being the latter responsible for the direct cytotoxicity against the epithelial cells. In latter stages the role of interleukin- 17 producing cells, apparently differently regulated compared with Crohn's disease, remains to be elucidated. Finally, human ulcerative colitis is characterized by the presence of various types of autoantibodies including pANCA, antibodies against goblet cells and the isoforms 1 and 5 of human tropomyosin. The pathogenic potential of these antibodies is still debated. The present review focus on new achievements in the various scenarios converging to the clinical and histopathological feature of ulcerative colitis.

Keywords: Microbiodata, Animal models, Innate immunity, Adaptive immunity, Mucosla barrier, Autoimmunity, Ulcerative Colitis, MUC2, Toll-like receptor, MyD88, ECAC, TRUC

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Article Details

VOLUME: 12
ISSUE: 10
Year: 2011
Page: [1373 - 1382]
Pages: 10
DOI: 10.2174/138945011796818261
Price: $58

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