Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine-mediated retention mechanism

Peter Middel ^1*, Dirk Raddatz ², Bastian Gunawan ¹, Florian Haller ¹ and Heinz-Joachim Radzun ¹

¹ Department of Pathology, Georg-August University of Göttingen, Germany
² Department of Gastroenterology, Georg-August University of Göttingen, Germany

^* To whom correspondence should be addressed. E-mail: pmiddel{at}med.uni-goettingen.de.

Accepted 7 August 2005

Abstract

Background & Aims: Activation of T-cells by dendritic cells is thought to play a pivotal role in the induction and maintenance of Crohn's disease. Detailed analyses, however, concerning the phenotype and maturation of dendritic cells as well as the mechanisms underlying their recruitment are still lacking for Crohn's disease.

Methods: The different myeloid and plasmacytoid DC subsets were characterized by immunohistochemistry. Expression of the so called "lymphoid" chemokines CCL19, CCL20, and CCL21 was determined by real-time RT-PCR in Crohn's disease and normal controls. Furthermore, the expression of CCL19, CCL20, and CCL21 as well as their receptors CCR6 (for CCL20) and CCR7 (for CCL19 and CCL21) was characterized by immunohistochemistry and in addition, their cellular localization was determined by double immunofluorescence investigations.

Results: Colonic tissue affected by Crohn's disease is characterized by an increased number of mature myeloid DC forming clusters with proliferating T cells. In keeping with their advanced maturation, dendritic cells posses the chemokine receptor CCR7. Increased expression of the CCR7 ligands CCL19 by DC themselves as well as CCL21 by reticular cells and lymphatic vessels was observed in Crohn's disease, thereby causing the matured dendritic cells to be trapped at the site of inflammation.

Conclusion: Our results demonstrate that autocrine and paracrine actions of lymphoid chemokines in Crohn's disease may lead to increased numbers of mature dendritic cells away from their usual migration to lymphoid organs and result in the development of a tertiary lymphatic tissue within the bowel wall maintaining the autoimmune inflammation in CD.

Keywords: Crohn's disease, chemokines, dendritic cells

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