The role of the innate immune system in microbially induced intestinal inflammation and neoplasia
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Inflammatory bowel disease (IBD) is one of the most common immune-mediated diseases in the United States costing the average patient tens of thousands of dollars annually, and greatly diminishing quality-of-life. While there is no universal cure for IBD, recently developed treatments targeting the immunological basis of disease have proven successful in managing clinical symptoms. However, these pharmaceutical therapies such as infliximab (Remicade[registered trademark]) carry several side effects and are not efficacious in all patients. Thus, more selective treatments are needed. One necessary step in the development of such agents is a more precise understanding of which cells in the gastrointestinal tract are primary contributors to the pathogenesis of IBD. We demonstrate that a rare subset of dendritic cells expressing CD8[alpha] is present in significantly different numbers in mouse strains considered susceptible or resistant to a microbially induced model of IBD. Additionally, we show that cells derived from the target organ of susceptible mice prior to and shortly after induction of the disease process are prone to production of greater levels of certain inflammatory mediators including IL-12/23p40, IP-10, RANTES, and TNF-[alpha]. Lastly, we describe the generation of a mouse strain susceptible to the disease model but selectively lacking the subset of dendritic cells expressing CD8[alpha], to be used in future studies. One of the most serious sequela to IBD is colitis-associated colorectal cancer (CAC). Diagnosis of colorectal cancer in general is reliant on tests that suffer from either poor sensitivity or specificity (such as fecal occult blood tests), or invasiveness (such as colonoscopy). Newer genetic tests have been developed for the identification of hereditary risk factors, however CAC follows a molecular pathway distinct from that of familial forms of colorectal cancer. Thus, the development of noninvasive screening assays for CAC with high sensitivity and specificity would increase compliance w
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.