Scientific Abstract

Proposal No.   IBD-0092R
Principal Investigator:  Konstantinos Papadakis, M.D.
Applicant Organization:   Cedars-Sinai Medical Center (Los Angeles, California, U.S.A.)
Project Title:  Phenotypic and functional characterization of CCR9+ T lymphocytes in small intestinal Crohn’s disease
Period of Award:  April 1, 2004 – December 31, 2005

Chemokines and their receptors play a critical role in the constitutive and inflammatory migration of lymphocytes to secondary lymphoid organs and peripheral tissues.  The CCL25/TECK and CCR9 ligand/receptor pair plays an important role in small intestinal (SI) immunity and inflammation.  Specifically, CCL25/TECK is upregulated in inflamed SI, but not colon, and CCR9, is detected in a higher percentage of circulating T cells in SI inflammatory diseases, such as Crohn’s disease (CD) and celiac disease.

The experiments in the proposal are designed to test the hypothesis that the CCR9 subset of T cells in the mucosal lymphoid tissues or peripheral blood has a predominant Th1 and/or reduction of the Tr1 component and are effector cells in SI CD.

In Aim I, we plan to characterize the phenotypic changes that occur in CCR9⁺ T cells during SI and colonic inflammation.  In Aim II, we plan to define the cytokine profile and potential regulatory function of the CCR9+ T cell subset in normal mucosal lymphoid tissue and in SI or colonic CD.

These studies will help clarify the role of CCR9⁺ T cells in CD, particularly small intestine CD and may lead to the development of new therapies for CD.