Scientific Abstract

Proposal No.   IBD-0053
Principal Investigator:  Chang H. Kim, Ph.D.
Applicant Organization:  Purdue University (West Lafayette, Indiana, U.S.A.)
Project Title:  CXCL16 and CXCR6 in Crohn’s disease
Period of Award:  February 1, 2003 - January 31, 2004

Crohn’s disease is characterized by aberrant type I polarized (Th1) inflammation and concomitant presence of activated CD4+ T cells in the lamina propria of intestinal tracts.  Chemokines expressed in specific microenvironments of tissues recruit T cells expressing cognate chemokine receptors from the circulation or nearby tissue sites.  Our preliminary data suggest that a chemokine receptor CXCR6 is preferentially expressed by activated type 1 or Th1 CD4+ T cells in the intestines and other tissues.  These CXCR6+ T cells are primarily localized in the lamina propria, and the chemokine ligand for the CXCR6 (CXCL16) is specifically expressed in Crohn’s disease, but not in normal tissues, suggesting that CXCL16 and CXCR6 may play a role in recruitment and localization of Th1 T cells in intestinal microenvironments as part of the pathogenesis of Crohn’s disease.

We propose to determine:  1) the expression of the chemokine receptor CXCR6 on T cells in Crohn’s disease and expression sites and conditions of its chemokine ligand, CXCL16, in Crohn’s disease tissues; 2) the role of CXCR6 and CXCL16 in T cell trafficking and localization of intestinal T cells in normal and Crohn’s disease tissues; 3) the roles of CXCR6 and CXCL16 in the progression of Crohn’s disease.
 
This project will reveal the anatomical sites of CXCL16 expression and of CXCR6+ T cell localization in Crohn’s disease and determine whether CXCL16 and CXCR6 are involved in the activated Th1 cell trafficking to the intestines and/or in the progression of Crohn’s disease.  Therefore, this project may provide information about the trafficking behavior of activated pathogenic intestinal T cells, and potentially reveal a point of therapeutic intervention in the progression of Crohn’s disease.