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

Andreas Muehlhoefer, Lawrence J. Saubermann, Xuibin Gu, Kerstin Luedtke-Heckenkamp, Ramnik Xavier, Richard S. Blumberg, Daniel K. Podolsky, Richard P. MacDermott, Hans Christian Reinecker

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195 Scopus citations

Abstract

Fractalkine is a unique chemokine that combines properties of both chemoattractants and adhesion molecules. Fractalkine mRNA expression has been observed in the intestine. However, the role of fractalkine in the healthy intestine and during inflammatory mucosal responses is not known. Studies were undertaken to determine the expression and function of fractalkine and the fractalkine receptor CX3CR1 in the human small intestinal mucosa. We identified intestinal epithelial cells as a novel source of fractalkine. The basal expression of fractalkine mRNA and protein in the intestinal epithelial cell line T-84 was under the control of the inflammatory mediator IL-1β. Fractalkine was shed from intestinal epithelial cell surface upon stimulation with IL-1β. Fractalkine localized with caveolin-1 in detergent-insoluble glycolipid-enriched membrane microdomains in T-84 cells. Cellular distribution of fractalkine was regulated during polarization of T-84 cells. A subpopulation of isolated human intestinal intraepithelial lymphocytes expressed the fractalkine receptor CX3CR1 and migrated specifically along fractalkine gradients after activation with IL-2. Immunohistochemistry demonstrated fractalkine expression in intestinal epithelial cells and endothelial cells in normal small intestine and in active Crohn's disease mucosa. Furthermore, fractalkine mRNA expression was significantly up- regulated in the intestine during active Crohn's disease. This study demonstrates that fractalkine-CX3CR1-mediated mechanism may direct lymphocyte chemoattraction and adhesion within the healthy and diseased human small intestinal mucosa.

Original languageEnglish (US)
Pages (from-to)3368-3376
Number of pages9
JournalJournal of Immunology
Volume164
Issue number6
DOIs
StatePublished - Mar 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Muehlhoefer, A., Saubermann, L. J., Gu, X., Luedtke-Heckenkamp, K., Xavier, R., Blumberg, R. S., Podolsky, D. K., MacDermott, R. P., & Reinecker, H. C. (2000). Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa. Journal of Immunology, 164(6), 3368-3376. https://doi.org/10.4049/jimmunol.164.6.3368