Expression and regulation of chemokine receptor CXCR3 (CD183) on human gastrointestinal stem cells (hGISC) derived primary epithelial cells

Abstract

Abstract Expression of Chemokine receptor CXCR3 (CD183) by cells in inflamed tissues play essential role in the development of chronic conditions by attracting leucocytes to the inflammatory sites. CXCR3 expression in intestinal epithelium has also been implicated in celiac disease by means of its potential role in peptide (gliadin) uptake and triggering of immune responses in the small intestine. Therefore, having an CXCR3 expressing intestinal epithelial cell system in long-term culture would be a valuable tool for discovery and development of new treatments for celiac and/or other gastrointestinal inflammatory diseases. Earlier, we have developed a method for growing human intestinal primary epithelial cells (HIPEC) from isolated human gastrointestinal stem cells (hGICSs) in long-term culture. Now we examined two small intestinal HIPEC lines for CXCR3 expression by immunocytochemical staining and subsequent fluorescence microscopic analysis. Our results showed that CXCR3 was either undetectable or weakly expressed in normal jejunal HIPECs that had columnar characteristics whereas CXCR3 was detected on HIPECs with enriched MUC2 positive goblet epithelial cells. CXCR3 was also detectable in HIPECs derived from an actively inflamed tissue from a patient with ulcerative colitis (UC). Stimulation of normal HIPECs with proinflammatory signaling agents LPS, TNFα or IFNγ showed a minimum effect on the level of CXCR3 expression when added individually. However combinations of LPS with either TNFa or IFNg or both increased the CXCR3 expression on HIPECs. These findings may help better understand of the disease mechanisms and development of new treatment for inflammatory conditions such as celiac disease and/or ulcerative colitis.