Novel markers of the human follicle-associated epithelium identified by genomic profiling and microdissection

ANDERLE P1*., RUMBO M1*., SIERRO F1,2., MANSOURIAN R3., MICHETTI P4., ROBERTS MA5, KRAEHENBUHL J.P1.

GASTROENTEROLOGY

Año: 2005 vol. 129 p. 321 - 321

0016-5085

Background and aims: Regulation of gene expression in the follicle-associated epithelium (FAE) over Peyer’s patches is largely unknown. CCL20, a chemokine that recruits immature dendritic cells is one of the few FAE specific markers described so far. Lymphotoxin beta (LT2) expressed on the membrane of immune cells triggers CCL20 expression in enterocytes. In this work we measured expression profiles of LT2 treated intestinal epithelial cells and selected CCL20 co-regulated genes in order to identify new FAE markers. Methods: Genomic profiles of T84 and Caco-2 cell lines treated either with LT2, flagellin or TNF were measured using the Affymetrix GeneChip U133A. Clustering analysis was used to select CCL20 co-regulated genes and laser dissection microscopy and real-time PCR on human biopsies was used to assess the expression of the selected markers. Results: Applying a two-way ANOVA we identified regulated genes upon the different treatments. A subset of genes involved in inflammation and related to the NFB pathway were co-regulated with CCL20. Among these genes, the anti-apoptotic factor TNFAIP3 was highly expressed in the FAE. CCL23, which was not co-regulated in vitro with CCL20 was also specifically expressed in the FAE.Conclusion: We have identified two novel human FAE-specifically expressed genes. Most of the CCL20-coregulated genes did not show FAE-specific expression, suggesting that other signaling pathways are critical to modulate FAE-specific gene expression.