The gastrointestinal epithelium plays a central role in maintaining and coordinating mucosal homeostasis and immunity. Intestinal epithelial barrier compromise in mucosal wounds is seen in many pathologic states that encompass inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. Coordinated epithelial cell migration and proliferation are crucial for mucosal wound closure, yet many aspects of this complex process are not well understood. Mucosal reparative events are orchestrated by the epithelium itself as well as by a spatiotemporal interplay of epithelial-immune cell cross-talk. Select inflammatory cytokines initiate synthesis of mediators that not only serve to influence the inflammatory cascade but also dismantle it and promote repair. The overarching hypothesis is that temporal recruitment and activation of immune cells into injured sites influence epithelial signaling to promote repair. Thus, the proposed studies will identify and characterize mechanisms by which immune cell derived mediators influence and regulate intestinal epithelial wound repair. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which inflammatory cell and epithelial mediators control intestinal epithelial homeostasis and mucosal wound repair. In the long term these studies will aid in the development of new therapeutic strategies aimed at promoting intestinal mucosal wound repair.
The lining of the gastrointestinal tract plays an important role in immune defense, which can be significantly compromised by conditions such as inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. This grant will address mechanisms by which the mucosal lining heals after such damage. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which wound healing is controlled, and in the long term, these studies will aid in the development of new therapeutic strategies aimed at promoting mucosal wound repair.
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