The Mechanisms of T Cell-Induced Mucosal Growth in the Gut

T cell immune reactions in the gut mucosa are associated with changes in mucosal shape. In the small bowel the stereotypic response is villus atrophy and crypt hyperplasia and in the colon it is mucosal thickening and crypt hyperplasia. <P>
Here we will use a new model of colitis elicited by the intimin of enteropathogenic E. coli transfected into the mouse pathogen Citrobacter rodentium, and colitic IL-2 knockout mice, to investigate the pathways by which activated T cells remodel colonic mucosa. We will focus on the production of epithelial growth factors, extracellular matrix production and degradation, and stromal cell proliferation during the evolution and resolution of intimin colitis.<P>
In addition we will use knockout mice (KGF, TGF alpha, MMP3 and TIMP-1) to determine which are the critical molecules in vivo.