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Dermal Fibroblasts Induce Maturation of Dendritic Cells¹

Anja Saalbach^2,*, Claudia Klein^*, Jonathan Sleeman, Ulrich Sack, Friederike Kauer^*, Carl Gebhardt^*, Marco Averbeck^*, Ulf Anderegg^* and Jan C. Simon^*

^* Department of Dermatology, Venerology, and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany; Institute of Clinical Immunology and Transfusion Medicine, Medical Faculty of Leipzig University, Leipzig, Germany; and Research Centre Karlsruhe, Institute of Toxicology and Genetics, Karlsruhe, Germany

To trigger an effective T cell-mediated immune response in the skin, cutaneous dendritic cells (DC) migrate into locally draining lymph nodes, where they present Ag to naive T cells. Little is known about the interaction of DC with the various cellular microenvironments they encounter during their migration from the skin to lymphoid tissues. In this study, we show that human DC generated from peripheral blood monocytes specifically interact with human dermal fibroblasts via the interaction of ₂ integrins on DC with Thy-1 (CD90) and ICAM-1 on fibroblasts. This induced the phenotypic maturation of DC reflected by expression of CD83, CD86, CD80, and HLA-DR in a TNF-- and ICAM-1-dependent manner. Moreover, fibroblast-matured DC potently induced T cell activation reflected by CD25 expression and enhanced T cell proliferation. Together these data demonstrate that dermal fibroblasts that DC can encounter during their trafficking from skin to lymph node can act as potent regulators of DC differentiation and function, and thus may actively participate in the regulation and outcome of DC-driven cutaneous immune responses.

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 the German Research Foundation (Deutsche Forschungsgemeinschaft SA863/1-3, Te284/2-2) and the Interdisciplinary Center of Clinical Research Leipzig at the Faculty of Medicine of the Universität Leipzig (Project Z14(INT05)).

² Address correspondence and reprint requests to Dr. Anja Saalbach, Department of Dermatology, Venerology, and Allergology, Medical Faculty of Leipzig University, Johannisallee 30, 04103 Leipzig, Germany. E-mail address: Anja.Saalbach{at}medizin uni-leipzig.de

³ Abbreviations used in this paper: DC, dendritic cell; CFDA, carboxyfluorescein diacetate succinimidyl ester; CHO, Chinese hamster ovary.

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