Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa

Fractalkine is a unique chemokine that combines properties of both chemoatt ractants and adhesion molecules, Fractalkine mRNA expression has been obser ved in the intestine. However, the role of fractalkine in the healthy intes tine and during inflammatory mucosal responses is not known, Studies were u ndertaken to determine the expression and function of fractalkine and the f ractalkine receptor CX(3)CR1 in the human small intestinal mucosa, Wt? iden tified intestinal epithelial cells as a novel source of fractalkine. The ba sal expression of fractalkine mRNA and protein in the intestinal epithelial cell line T-84 was under the control of the inflammatory mediator a-lp. Fr actalkine was shed from intestinal epithelial cell surface upon stimulation with IL-IP. Fractalkine localized with caveolin-1 in detergent-insoluble g lycolipid-enriched membrane microdomains in T-84 cells. Cellular distributi on of fractalkine was regulated during polarization of T-84 cells. A subpop ulation of isolated human intestinal intra-epithelial lymphocytes expressed the fractalkine receptor CX(3)CR1 and migrated specifically along fractalk ine gradients after activation with IL-2, Immunohistochemistry demonstrated fractalkine expression in intestinal epithelial cells and endothelial cell s in normal small intestine and in active Crohn's disease mucosa, Furthermo re, fractalkine mRNA expression was significantly up-regulated in the intes tine during active Crohn's disease, This study demonstrates that fractalkin e-CX(3)CR1-mediated mechanism may direct lymphocyte chemoattraction and adh esion within the healthy and diseased human small intestinal mucosa.