HOME
Return to Table of Contents
THE CXCL13 CHEMOKINE IS EXPRESSED IN PANETH CELLS AND IS REGULATED BY THE TRANSCRIPTION FACTOR CUTL1
M Darsigny, F Boudreau
Département d’anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke
Chemokines, like CXCL13, participate in leukocytes trafficking, gut-associated lymphoid tissue (GALT) establishment and inflammatory processes. It was proposed recently that CXCL13 can also promote growth of CXCR5 expressing colorectal cells in vitro. CXCR5 was also shown to be expressed in pancreatic and colon cancer.
AIM: To verify whether CXCR5’s ligand CXCL13 is expressed by the intestinal epithelium.
METHODS: CXCL13 expression was monitored in cultured epithelial cell lines and its expression localized using indirect immunofluorescence on mouse tissue.
RESULTS: First, CXCL13 mRNA was detected in HIEC and IEC cell lines by RT-PCR. We next verified whether CXCL13 expression could vary during differentiation. IEC6L1 were co-cultured on mesenchymal cell and we confirmed an up-regulated expression of CXCL13 upon differentiation. We then verified the localization of the chemokine by using indirect immunofluorescence on intestinal mouse tissue. This analysis revealed that Paneth cells were strongly positive for Cxcl13 signal within their granules. To see if known epithelial transcription factors could regulate Cxcl13 expression, we further analyzed the promoter with the TRANSFAC database. This revealed the presence of 3 Cutl1 binding sites within 1 kb. By EMSA, two out of the three sites were found positive for Cutl1 binding. IEC6L1 with Cutl1 expression knocked down by shRNA were next used to reinforce this relationship. When Cutl1 expression was reduced by 60%, Cxcl13 expression was reduced by 84%. Finally, Cutl1 mutant mice displayed a 60% reduction of Cxcl13 expression in the intestine.
CONCLUSIONS: To our knowledge, this is the first suggestion of CXCL13 expression by the gut epithelium. We are currently looking at CXCR5 expression in intestinal epithelial cells and assessing the role of the CXCL13-CXCR5 couple in the gut epithelium homeostasis.
Supported by the CCFC