407
views
0
recommends
+1 Recommend
0 collections
    8
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Genome-wide expression profiling of mouse and human leukocytes reveal conserved transcriptional programs of plasmacytoid or conventional dendritic cell subsets.

          Abstract

          Background

          Dendritic cells (DCs) are a complex group of cells that play a critical role in vertebrate immunity. Lymph-node resident DCs (LN-DCs) are subdivided into conventional DC (cDC) subsets (CD11b and CD8α in mouse; BDCA1 and BDCA3 in human) and plasmacytoid DCs (pDCs). It is currently unclear if these various DC populations belong to a unique hematopoietic lineage and if the subsets identified in the mouse and human systems are evolutionary homologs. To gain novel insights into these questions, we sought conserved genetic signatures for LN-DCs and in vitro derived granulocyte-macrophage colony stimulating factor (GM-CSF) DCs through the analysis of a compendium of genome-wide expression profiles of mouse or human leukocytes.

          Results

          We show through clustering analysis that all LN-DC subsets form a distinct branch within the leukocyte family tree, and reveal a transcriptomal signature evolutionarily conserved in all LN-DC subsets. Moreover, we identify a large gene expression program shared between mouse and human pDCs, and smaller conserved profiles shared between mouse and human LN-cDC subsets. Importantly, most of these genes have not been previously associated with DC function and many have unknown functions. Finally, we use compendium analysis to re-evaluate the classification of interferon-producing killer DCs, lin -CD16 +HLA-DR + cells and in vitro derived GM-CSF DCs, and show that these cells are more closely linked to natural killer and myeloid cells, respectively.

          Conclusion

          Our study provides a unique database resource for future investigation of the evolutionarily conserved molecular pathways governing the ontogeny and functions of leukocyte subsets, especially DCs.

          Related collections

          Most cited references 73

          • Record: found
          • Abstract: found
          • Article: not found

          DAVID: Database for Annotation, Visualization, and Integrated Discovery.

          Functional annotation of differentially expressed genes is a necessary and critical step in the analysis of microarray data. The distributed nature of biological knowledge frequently requires researchers to navigate through numerous web-accessible databases gathering information one gene at a time. A more judicious approach is to provide query-based access to an integrated database that disseminates biologically rich information across large datasets and displays graphic summaries of functional information. Database for Annotation, Visualization, and Integrated Discovery (DAVID; http://www.david.niaid.nih.gov) addresses this need via four web-based analysis modules: 1) Annotation Tool - rapidly appends descriptive data from several public databases to lists of genes; 2) GoCharts - assigns genes to Gene Ontology functional categories based on user selected classifications and term specificity level; 3) KeggCharts - assigns genes to KEGG metabolic processes and enables users to view genes in the context of biochemical pathway maps; and 4) DomainCharts - groups genes according to PFAM conserved protein domains. Analysis results and graphical displays remain dynamically linked to primary data and external data repositories, thereby furnishing in-depth as well as broad-based data coverage. The functionality provided by DAVID accelerates the analysis of genome-scale datasets by facilitating the transition from data collection to biological meaning.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.

            Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Regulatory T cell lineage specification by the forkhead transcription factor foxp3.

              Regulatory T cell-mediated dominant tolerance has been demonstrated to play an important role in the prevention of autoimmunity. Here, we present data arguing that the forkhead transcription factor Foxp3 acts as the regulatory T cell lineage specification factor and mediator of the genetic mechanism of dominant tolerance. We show that expression of Foxp3 is highly restricted to the subset alphabeta of T cells and, irrespective of CD25 expression, correlates with suppressor activity. Induction of Foxp3 expression in nonregulatory T cells does not occur during pathogen-driven immune responses, and Foxp3 deficiency does not impact the functional responses of nonregulatory T cells. Furthermore, T cell-specific ablation of Foxp3 is sufficient to induce the identical early onset lymphoproliferative syndrome observed in Foxp3-deficient mice. Analysis of Foxp3 expression during thymic development suggests that this mechanism is not hard-wired but is dependent on TCR/MHC ligand interactions.
                Bookmark

                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central
                1465-6906
                1465-6914
                2008
                24 January 2008
                : 9
                : 1
                : R17
                Affiliations
                [1 ]CIML (Centre d'Immunologie de Marseille-Luminy), Université de la Méditerranée, Parc scientifique de Luminy case 906, Marseille F-13288, France
                [2 ]U631, INSERM (Institut National de la Santé et de la Recherche Médicale), Parc scientifique de Luminy case 906, Marseille F-13288, France
                [3 ]UMR6102, CNRS (Centre National de la Recherche Scientifique), Parc scientifique de Luminy case 906, Marseille F-13288, France
                [4 ]Hematopoiesis and leukemogenesis in the mouse, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), rue Laurent Fries, ILLKIRCH F-67400, France
                [5 ]U596, INSERM, rue Laurent Fries, ILLKIRCH F-67400, France
                [6 ]UMR7104, CNRS, rue Laurent Fries, ILLKIRCH F-67400, France
                [7 ]UM41, Université Louis Pasteur, rue Laurent Fries, Strasbourg F-67400, France
                [8 ]The Medical Investigation of Neurodevelopmental Disorders Institute, University of California at Davis Medical Center, Sacramento, CA 95817, USA
                [9 ]Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Boulevard Baille, Marseille F-13385, France
                [10 ]Current address: Genomics Institute of the Novartis Research Foundation, John Jay Hopkins Drive, San Diego, CA 92121, USA
                Article
                gb-2008-9-1-r17
                10.1186/gb-2008-9-1-r17
                2395256
                18218067
                Copyright © 2008 Robbins et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research

                Genetics

                Comments

                Comment on this article