: (NO THESIS SELECTED) Intestinal epithelial cells (IECs), provide a physical and immunologic barrier against the external environment and area key aspect in the pathogenesis of Inflammatory Bowel Disease (IBD). Upon infection with enteric pathogens, IECs produce cytokines and antibacterial factors. Toll like receptors (TLRs) on cells of the innate immune system recognize conserved microbial patterns but the functions of TLRs on IECs remain unclear. In our lab, we are determining the expression of TLR1-5 on human intestinal epithelium using immunohistochemistry of intestinal sections derived from surgical resections. A crypt cell demonstrating strong immunoreactivity for the specific combination of TLR1 and TLR2 was identified. My present research is to study the functional significance of TLR1 and TLR2 co-expression in a variety of cell lines. TLR 1 expression in transiently transfected 293T and DLD- 1 cells does not activate a NF-kB reporter. Co-expression of TLR1 and TLR2 in LPS-treated 293T and DLD-1 cells leads to a strong synergistic activation of an NF-kB reporter. TLR1 appears to specifically interact with TLR2, as co-expression of TLR1 and TLR4 does not activate NF-kB to a greater extent than TLR4 alone. I propose to study a human intestinal crypt epithelial cell that co-expresses TLR1 and TLR2. TLR1 and TLR2 may functionally interact to activate NF-kB and inflammatory gene expression in IECs. To research the mechanism and function of TLR interactions in host defense against enteric pathogens and in mucosal inflammation, morphological and functional characterization of this epithelial cell type and mechanisms of synergy between TLR1 and TLR2 will be investigated.
