Published online before print December 18, 2008

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Copyright © 2009 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2009.080273

Accepted for publication September 30, 2008.

Article

CD83⁺CCR7^- Dendritic Cells Accumulate in the Subepithelial Dome and Internalize Translocated Escherichia coli HB101 in the Peyer's Patches of Ileal Crohn's Disease

Sa'ad Y. Salim^*, Manuel A. Silva, Åsa V. Keita^*, Marie Larsson, Peter Andersson, Karl-Eric Magnusson^¶, Mary H. Perdue, and Johan D. Söderholm^*@

From the Divisions of Surgery,* Molecular Virology, and Medical Microbiology,^¶ Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; the Intestinal Disease Research Programme, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; and the Division of Colorectal Surgery, Department of Surgery, University Hospital, Linköping, Sweden

^@ To whom correspondence should be addressed. E-mail: johda{at}ibk.liu.se.

	Abstract

Recurrent Crohn's disease originates with small erosions in the follicle-associated epithelium overlying the Peyer's patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohn's disease. Ileal tissues were obtained after surgery performed on Crohn's patients; ileal samples from noninflammatory bowel disease and ulcerative colitis served as standard and inflammatory controls, respectively. Flow cytometry of isolated intestinal mononuclear cells showed a larger subset of dendritic cells in Crohn's samples compared with controls. This finding was corroborated by confocal microscopy, showing enhanced infiltrates of cells positive for the dendritic cell markers, DC-SIGN⁺ and CD83⁺, in the subepithelial dome. Moreover, the CD83⁺ cells in Crohn's tissues showed reduced expression of the lymph node migratory receptor, CCR7, possibly contributing to the high numbers of dendritic cells. After exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in the subepithelial dome of Crohn's disease demonstrated increased co-localization with translocated bacteria. Immunohistochemical results revealed that DC-SIGN⁺ cells in Crohn's tissues were found to express toll-like receptor 4 and produce tumor necrosis factor-. In conclusion, nonmigrating dendritic cells that accumulate in the subepithelial dome and internalize nonpathogenic bacteria may be important for the onset and perpetuation of mucosal inflammation in Crohn's disease.