Patients with ulcerative colitis (UC), a form of inflammatory bowel disease, have chronic inflammation of the intestine caused by dysfunctional immune responses and disruption of the colon’s epithelial cell lining.
In previous studies, Michael Rosen, M.D., MSCI, assistant professor of Pediatrics, and colleagues demonstrated increased levels of activated STAT6 – a protein that participates in immune cell signaling – in the intestines of children with UC. Now, they have explored the role of STAT6 in UC using a mouse model that mimics the immunological characteristics of the human disease. They induced colitis in wild-type (normal) mice and in mice missing STAT6. The STAT6-deficient mice had reduced colitis compared to wild-type, and had improvements in weight, colon length and histopathology. The STAT6-deficient mice also had reduced expression of an epithelium-disrupting protein (claudin-2) and of factors that induce “Th2”-type immune responses.
The findings, reported Feb. 15 in the Journal of Immunology, implicate STAT6 in the pathogenesis of colitis in vivo and suggest that it may be a promising target for UC drug development.
This research was supported by grants from the National Institutes of Health (AT004821, HD061607) and by a Merit Review grant from the Department of Veterans Affairs, a North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Foundation Award, a Vanderbilt Physician Scientist Development Award and the Vanderbilt Digestive Diseases Research Center (DK058404).
