Final Progress Report

Proposal No. IBD-0185
Principal Investigator:  Steven F. Zeigler, Ph.D.
Applicant Organization:  Benaroya Research Institute at Virginia Mason (Seattle, Washington, U.S.A.)
Project Title:   Regulatory T cells in inflammatory bowel disease
Period of Award:  August 1, 2006 – May 31, 2008

Lay Summary of Final Progress Report

Regulatory T cells (Tregs) play a critical role in limiting inflammation in the bowel.  Therefore, we sought to find a defect in these cells in patients with inflammatory bowel disease (IBD) which might explain how IBD occurs.  We did not find Tregs to be deficient in number, character, or function in IBD patients, but instead found them to be at least as common as they are in the bowels of patients without IBD.  However, we found that they lost their ability to inhibit other cells of the immune system if they were cultured with certain cells present in the bowels of patients with IBD.  This loss of Treg function was not seen when cells from the bowels of patients without IBD were used instead.  The cells responsible for compromising Treg function in our experiments appear to be a type of antigen presenting cell called a plasmacytoid dendritic cell (pDC).  While pDC are rare in the colons of patients without IBD, they appear to be selectively enriched in the inflamed intestines of some IBD patients.  Current efforts are directed towards further characterizing these cells, and defining a mechanism by which they subvert Treg inhibitory function.  The latter could raise an attractive target for therapy aimed at bringing the intestinal inflammation of IBD under control.