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      Blood-derived dermal langerin + dendritic cells survey the skin in the steady state

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          Abstract

          Langerin is a C-type lectin receptor that recognizes glycosylated patterns on pathogens. Langerin is used to identify human and mouse epidermal Langerhans cells (LCs), as well as migratory LCs in the dermis and the skin draining lymph nodes (DLNs). Using a mouse model that allows conditional ablation of langerin + cells in vivo, together with congenic bone marrow chimeras and parabiotic mice as tools to differentiate LC- and blood-derived dendritic cells (DCs), we have revisited the origin of langerin + DCs in the skin DLNs. Our results show that in contrast to the current view, langerin +CD8 DCs in the skin DLNs do not derive exclusively from migratory LCs, but also include blood-borne langerin + DCs that transit through the dermis before reaching the DLN. The recruitment of circulating langerin + DCs to the skin is dependent on endothelial selectins and CCR2, whereas their recruitment to the skin DLNs requires CCR7 and is independent of CD62L. We also show that circulating langerin + DCs patrol the dermis in the steady state and migrate to the skin DLNs charged with skin antigens. We propose that this is an important and previously unappreciated element of immunosurveillance that needs to be taken into account in the design of novel vaccine strategies.

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          Most cited references39

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          Chemokines: a new classification system and their role in immunity.

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            Mouse and human dendritic cell subtypes.

            Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.
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              Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids

              Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein–coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42–p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                24 December 2007
                : 204
                : 13
                : 3133-3146
                Affiliations
                [1 ]Department of Gene and Cell Medicine and [2 ]Department of Medicine, Mount Sinai School of Medicine, Mount Sinai School of Medicine, New York, NY 10029
                [3 ]Unidad de Imunologia de Transplantes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Madrid, Spain
                [4 ]Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale U631, Centre National de la Recherche Scientifique UMR6102, Université de la Méditerrannée, 13288 Marseille Cedex 9, France
                Author notes

                CORRESPONDENCE Miriam Merad: Miriam.Merad@ 123456mssm.edu

                Article
                20071733
                10.1084/jem.20071733
                2150983
                18086862
                11f0785e-168d-4625-b65c-c75f1e10b125
                Copyright © 2007, The Rockefeller University Press
                History
                : 14 August 2007
                : 21 November 2007
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                Medicine
                Medicine

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