Caudal-related homeobox transcription factor 2 (CDX2). CDX2 is a nuclear transcription factor that is essential for regulating genes related to epithelial functions [5-11] and controlling the balance between differentiation and proliferation of IECs

BACKGROUND Introduction The intestinal epithelium is the most vigorously self-renewing tissue of adult mammals and consists of four well-characterised types of differentiated cells: absorptive enterocyte cells (or colonocytes in the large intestine), mucus-secreting goblet cells, enteroendocrine cells and antimicrobial peptide producing Paneth cells (specialised cells in the epithelium of the small intestine) [1,2]. Three additional subtypes of intestinal epithelial cells (IECs) have been discovered recently: M cells, cup cells, and Tuft cells [3]; however, their functions remain largely unknown. The continuous renewal of the intestinal epithelium causes a number of unique challenges. Thus rates of intestinal cell production must be precisely balanced by cell loss. Perturbations in this balance will compromise epithelial barrier function or, alternatively, result in the development of intestinal disorders [4]. Cell proliferation and differentiation are thus tightly controlled in the normal intestinal epithelium. Various genes and transcription factors may take part in this process, in which some are up-regulated and others are down-regulated. One of these well-studied factors is the Caudal-related homeobox transcription factor 2 (CDX2). CDX2 is a nuclear transcription factor that is essential for regulating genes related to epithelial functions [5-11] and controlling the balance between differentiation and proliferation of IECs [12]. Thus loss of accurate control of CDX2 expression has been demonstrated to cause a serious disruption in the mucosal architecture, leading to intestinal diseases and developmental disorders. In addition, accumulated knowledge indicates that CDX2 may be pivotal in intestinal inflammation. In fact, a linkage between the key pathways involved in inflammation and regulators of homeostasis is often seen [13,14], supporting the hypothesis that there might be a connection between intestinal inflammation and CDX2 expression. This PhD thesis explores the role of CDX2 in inflammatory bowel disease (IBD) and investigates the impact of proinflammatory pathways on CDX2 expression and its target genes.