Lay Summary

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 an abnormal inflammatory response possibly caused by a subset of activated lymphocytes (T cells) in the intestinal tracts.  Chemokines are biologically active molecules expressed in specific tissues that recruit T cells from the blood and other tissues.  Our preliminary data suggest that a chemokine receptor, CXCR6, is preferentially expressed by the type of activated T cells in Crohn’s disease.  These CXCR6+ T cells are primarily localized in a specialized intestinal compartment called “lamina propria.”  Furthermore, the chemokine that activates this receptor (called CXCL16) is specifically expressed in Crohn’s disease tissues, but not in normal tissues, suggesting the possibility that this molecule and its receptor may play a role in recruitment and localization of the activated T cells in intestinal microenvironments during pathogenesis of Crohn’s disease.

We propose to determine:

1)   the expression of the chemokine CXCL16 and its receptor CXCR6 in Crohn’s disease tissues;
2)   the role of CXCR6 and CXCL16 in regulating T cell movement 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 they are involved in activated T cell trafficking to the intestines and/or in the progression of Crohn’s disease.  Therefore, this project may provide valuable information in understanding the abnormal infiltration of activated pathogenic T cells, and potentially reveal a point of therapeutic intervention in the progression of Crohn’s disease.