Selective regulation of epithelial gene expression in rabbit Peyer's patch tissue.

ABSTRACT

The physiological mechanisms that regulate epithelial gene expression during enterocyte migration and differentiation are still poorly understood. The present study has used a combination of quantitative in situ hybridisation, immunohistochemistry and enzyme cytochemistry to examine epithelial cell differentiation in rabbit small intestine. We have measured and compared the levels of mRNA and enzyme activity of the enterocyte brush border markers alkaline phosphatase, amino-peptidase N and lactase in normal villus epithelia and in epithelial cells exposed directly to the Peyer's patch immune environment. All three genes appeared to be expressed in parallel, but in each epithelial population examined, the pattern of gene expression was different. The level of these mRNAs was markedly reduced in Peyer's patch-associated epithelia, this being most pronounced in the follicle-associated epithelium, compared with normal villi. The activities of alkaline phosphatase and aminopeptidase N approximated the expression of their genes, whereas additional post-transcriptional events were shown to clearly contribute to the level of lactase activity in these tissues. These findings demonstrate that the reduced brush border hydrolase activity in Peyer's patch tissue that has been observed previously, is due to a down-regulation of epithelial gene expression in this location. These observations have been used to discuss epithelial differentiation in Peyer's patch tissue and the possible role of local immune factors in regulating such events.