Lay Summary

Proposal No.   IBD-0035
Principal Investigator: Stanford Peng, M.D., Ph.D.
Applicant Organization:  Washington University (St. Louis, Missouri, U.S.A.)
Project Title:  The roles of NFATs and innate immunity in intestinal inflammation
Period of Award:  October 1, 2002 - September 30, 2003

The cause of Crohn's disease and ulcerative colitis (Inflammatory Bowel Disease-IBD) remains largely unknown.  Recent studies have drawn attention to the role of the innate immune system, which includes cells like neutrophils and macrophages, in disease pathogenesis.  We have recently discovered a fascinating role for the nuclear factor of activated T cells (NFAT) protein family in IBD and innate immunity.  These proteins are transcription factors that regulate the expression of many immunity genes.  Animals that bear mutant forms of the NFAT proteins spontaneously develop IBD due to unregulated innate immunity, demonstrating that the NFAT proteins are critical in regulating inflammation in the intestine.  We are in the process of further characterizing these animals, to identify specifically what immune cell types are responsible for the disease, and how they do it.  We are particularly excited about these studies since the NFAT proteins have historically been highly amenable to pharmacological manipulation, such as with the drugs cyclosporin A and FK506; and therefore anticipate that our investigations will not only improve our understanding of the inflammatory process of IBD, but could also provide the basis for novel therapeutic options in IBD.