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Cutting Edge: Instructive Role of Peripheral Tissue Cells in the Imprinting of T Cell Homing Receptor Patterns¹

Fanny Edele^*,, Rosalie Molenaar, Dominique Gütle, Jan C. Dudda^¶, Thilo Jakob^*, Bernhard Homey^||, Reina Mebius, Mathias Hornef and Stefan F. Martin^2,*

^* Allergy Research Group, Department of Dermatology, University Medical Center, and Faculty of Biology, University of Freiburg, Freiburg, Germany; Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands; Department of Medical Microbiology and Hospital Hygiene, Medizinische Hochschule Hannover, Hannover, Germany; ^¶ Benaroya Research Institute, Seattle, WA 98101; and ^|| Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany

Tissue-specific homing of effector and memory T cells to skin and small intestine requires the imprinting of specific combinations of adhesion molecules and chemokine receptors by dendritic cells in the draining lymph nodes. In this study, we demonstrate that CD8⁺ T cells activated by Ag-pulsed bone marrow-derived dendritic cells were induced to express the small intestine homing receptors ₄β₇ integrin and chemokine receptor CCR9 in coculture with small intestinal epithelial cells. In contrast, in coculture with dermal fibroblasts the skin-homing receptor E-selectin ligand was induced. Interestingly, the imprinting of gut homing receptors on anti-CD3/anti-CD28 stimulated T cells was induced by soluble factors produced by small intestinal epithelial cells. Retinoic acid was identified as a crucial factor. These findings show that peripheral tissue cells directly produce homing receptor imprinting factors and suggest that dendritic cells can acquire their imprinting potential already in the peripheral tissue of origin.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Deutsche Forschungsgemeinschaft Grants MA1567/8-1 (to S.F.M.) and HO2236/5-2 (to M.H.), Swedish Research Council Grant K2003-31P-14792 (to M.H.), and Thyssen Foundation Grant AZ 10.05.2.173 (to M.H.).

² Address correspondence and reprint requests to Dr. Stefan F. Martin, Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany. E-mail address: stefan.martin{at}uniklinik-freiburg.de

³ Abbreviations used in this paper: DC, dendritic cell; BM-DC, bone marrow-derived DC; CM, conditioned medium; CT, cycle threshold; E-lig, E-selectin ligand; MLN, mesenteric lymph nodes; PP, Peyer’s patch; RA, retinoic acid; RALDH, retinal dehydrogenase; RAR, RA receptor; RXR, retinoid X receptor; SIEC, small intestinal epithelial cell.

⁴ The online version of this article contains supplemental material.