The mucosal lining of the lungs and gastrointestinal tract plays a pivotal role in the detection and elimination of invading pathogens. However, the immune system must be regulated in order to prevent damage to host tissue as dysregulated immune responses may result in severe pathology and subsequent disease. In particular, uncontrolled expansion of T helper (TH) 17 populations has been implicated in numerous inflammatory diseases such as myocarditis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and asthma. Interleukin (IL)-25 (IL-17E) is a recently described member of the IL-17 cytokine family. Recent studies have demonstrated key functions of IL-25 in TH2 cytokine-mediated host protective immunity and in the inhibition of IL-17-mediated intestinal inflammation. Despite an understanding of its biological relevance, little is known about the functional biology of IL-25. Understanding these regulatory pathways and how they relate to mucosal immunity will better enable the scientific community to develop targeted therapeutics for multiple inflammatory diseases. It has been proposed that IL-25-producing T cells represent a novel T helper cell subset, however, the cellular sources of IL-25 and the phenotypic characteristics of IL-25+ T cells are poor understood. Additionally, the mechanism by which IL-25 inhibits IL-17-mediated intestinal inflammation remains unknown. To address these questions, a murine model of intestinal inflammation, using the gastrointestinal helminth Trichuris muris, will be utilized. Analyses will be performed with a variety of molecular techniques, including flow cytometry, ELISAs, Western blots, and real time PCR. (Millions of people worldwide are affected by autoimmune and inflammatory diseases, such as allergies, asthma, and rheumatoid arthritis. These diseases represent uncontrolled expansion of cells of the immune system. Understanding the regulation of immune responses will impact public health on a global scale.)
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