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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900908v1 183/8/5069    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Kaden, S. A. Articles by Winkels, G. PubMed PubMed Citation Articles by Kaden, S. A. Articles by Winkels, G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Enhanced Dendritic Cell-Induced Immune Responses Mediated by the Novel C-Type Lectin Receptor mDCAR1

Stefan A. Kaden,^1* Stefanie Kurig,^* Katrin Vasters,^* Kay Hofmann,^* Kurt S. Zaenker, Juergen Schmitz,^* and Gregor Winkels^1*

^*Miltenyi Biotec, Bergisch Gladbach, Germany; and Institute of Immunology, University of Witten/Herdecke, Witten, Germany

The dendritic cell (DC) immunoreceptors (DCIR) and DC-immunoactivating receptors (DCAR) represent a subfamily of cell surface C-type lectin receptors (CLR), whose multifunctional capacities range from classical Ag uptake and immunoregulatory mechanisms to the involvement in DC ontogeny. On the basis of the generation of specific mAbs, we functionally characterized mouse DCAR1 (mDCAR1) as a member of the DCIR/DCAR family. Expression of mDCAR1 was strongly tissue dependent. mDCAR1 expression on DCs was restricted to the CD8⁺ DC subset in spleen and thymus and on subpopulations of CD11b⁺ myeloid cells in bone marrow and spleen, whereas the molecule was not detectable on both cell types in lymph nodes and peripheral blood. With respect to the function of CLRs as pattern recognition receptors, Ag delivered via mDCAR1 was internalized, was trafficked to early and late endosomes/lysosomes and, as a consequence, induced cellular and humoral responses in vivo even in the absence of CD40 stimulation. Intriguingly, upon triggering mDCAR1, CD8⁺ DCs increased the secretion of bioactive IL-12, whereas IL-10 release is markedly reduced, thereby indicating that Ag recognized by mDCAR1 induces enhanced proinflammatory responses. These data indicate that mDCAR1 is a functional receptor on cells of the immune system and provides further insights into the regulation of immune responses by CLRs.

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 Address correspondence and reprint requests to Dr. Stefan Alexander Kaden or Dr. Gregor Winkels, Miltenyi Biotec, Friedrich-Ebert-Strasse 68, D-51429 Bergisch-Gladbach, Germany. E-mail address: StefanK{at}miltenyibiotec.de or GregorW{at}miltenyibiotec.de

² Abbreviations used in this paper: CLEC, C-type lectin; CTLD, CLEC-like domain; CLR, CLEC receptor; APLEC, Ag-presenting CLR gene complex; DC, dendritic cell; DCIR, DC immunoreceptor; DCAR, DC immunoactivating receptor; PDC, plasmacytoid DC; CHO, Chinese hamster ovary; RBL, rat basophilic leukemia; h, human; r, rat; m; mouse (h, r, and m in combinations).

³ The online version of this article contains supplemental material.