Inflammatory bowel disease (IBD) causes significant human morbidity. A new area of research is to investigate gene regulation from unconventional portions of the genome, such as the newly identified long noncoding RNAs (lncRNAs). These new players have been implicated in many cellular processes. However, their role in inflammatory disease such as IBD has yet to be determined. The laboratories of the two Principal Investigators on this proposal have recently converged to identify a particular lncRNA, termed IFNG-AS1 or NeST lncRNA, in IBD susceptibility. In humans, this lncRNA is increased in abundance in IBD patients. In mice, it is the causative molecule in a classically defined viral susceptibility locus which we have collaboratively shown to protect against chemically induced murine colitis. Continuing to work together, we will test the role of this lncRNA in inflammatory pathogenesis, with the goal of developing new therapeutic and diagnostic tools to tackle IBD.