Scientific Abstract

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

Investigations of inflammation in the inflammatory bowel diseases (IBD) have traditionally focused upon the role of T and B lymphocytes, though recent studies suggest a growing importance of innate immune mechanisms, including neutrophils and macrophages.  We have recently discovered an intriguing role for the NFAT family of transcription factors in intestinal inflammation:  in the absence of lymphocytes, NFAT-mutant animals develop severe inflammatory bowel disease, suggesting that the NFAT proteins regulate innate intestinal immunity, and furthermore that lymphocytes, including T and/or B cells, suppress innate inflammation in the gut.  To our knowledge, these findings represent the first definitive evidence for lymphocyte-independent intestinal inflammation, as well as for the role of the NFAT proteins in intestinal immunity. In this application, we propose to fully characterize this IBD syndrome clinically and cellularly and explore the regulatory role of NFAT in preventing IBD.