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Transcriptional Profiling of Human Dendritic Cell Populations and Models - Unique Profiles of In Vitro Dendritic Cells and Implications on Functionality and Applicability

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      Abstract

      Background

      Dendritic cells (DCs) comprise heterogeneous populations of cells, which act as central orchestrators of the immune response. Applicability of primary DCs is restricted due to their scarcity and therefore DC models are commonly employed in DC-based immunotherapy strategies and in vitro tests assessing DC function. However, the interrelationship between the individual in vitro DC models and their relative resemblance to specific primary DC populations remain elusive.

      Objective

      To describe and assess functionality and applicability of the available in vitro DC models by using a genome-wide transcriptional approach.

      Methods

      Transcriptional profiling was performed with four commonly used in vitro DC models (MUTZ-3-DCs, monocyte-derived DCs, CD34-derived DCs and Langerhans cells (LCs)) and nine primary DC populations (dermal DCs, LCs, blood and tonsillar CD123 +, CD1c + and CD141 + DCs, and blood CD16 + DCs).

      Results

      Principal Component Analysis showed that transcriptional profiles of each in vitro DC model most closely resembled CD1c + and CD141 + tonsillar myeloid DCs (mDCs) among primary DC populations. Thus, additional differentiation factors may be required to generate model DCs that more closely resemble other primary DC populations. Also, no model DC stood out in terms of primary DC resemblance. Nevertheless, hierarchical clustering showed clusters of differentially expressed genes among individual DC models as well as primary DC populations. Furthermore, model DCs were shown to differentially express immunologically relevant transcripts and transcriptional signatures identified for each model DC included several immune-associated transcripts.

      Conclusion

      The unique transcriptional profiles of in vitro DC models suggest distinct functionality in immune applications. The presented results will aid in the selection of an appropriate DC model for in vitro assays and assist development of DC-based immunotherapy.

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      Most cited references 74

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

      Java Treeview--extensible visualization of microarray data.

      Open source software encourages innovation by allowing users to extend the functionality of existing applications. Treeview is a popular application for the visualization of microarray data, but is closed-source and platform-specific, which limits both its current utility and suitability as a platform for further development. Java Treeview is an open-source, cross-platform rewrite that handles very large datasets well, and supports extensions to the file format that allow the results of additional analysis to be visualized and compared. The combination of a general file format and open source makes Java Treeview an attractive choice for solving a class of visualization problems. An applet version is also available that can be used on any website with no special server-side setup.
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        • Record: found
        • Abstract: found
        • Article: not found

        Open source clustering software.

        We have implemented k-means clustering, hierarchical clustering and self-organizing maps in a single multipurpose open-source library of C routines, callable from other C and C++ programs. Using this library, we have created an improved version of Michael Eisen's well-known Cluster program for Windows, Mac OS X and Linux/Unix. In addition, we generated a Python and a Perl interface to the C Clustering Library, thereby combining the flexibility of a scripting language with the speed of C. The C Clustering Library and the corresponding Python C extension module Pycluster were released under the Python License, while the Perl module Algorithm::Cluster was released under the Artistic License. The GUI code Cluster 3.0 for Windows, Macintosh and Linux/Unix, as well as the corresponding command-line program, were released under the same license as the original Cluster code. The complete source code is available at http://bonsai.ims.u-tokyo.ac.jp/mdehoon/software/cluster. Alternatively, Algorithm::Cluster can be downloaded from CPAN, while Pycluster is also available as part of the Biopython distribution.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha

          Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.
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            Author and article information

            Affiliations
            [1 ]Department of Immunotechnology, Lund University, Lund, Sweden
            [2 ]Environmental Risk and Health Unit, Flemish Institute for Technological Research (VITO), Mol, Belgium
            [3 ]Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
            [4 ]Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands
            University of Bergen, Norway
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            Conceived and designed the experiments: KL ML. Performed the experiments: KL ML AA IN SS. Analyzed the data: KL ML AA. Contributed reagents/materials/analysis tools: KL AA IN SS TDG SG ML . Wrote the paper: KL AA IN SS TDG SG ML.

            Contributors
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, USA )
            1932-6203
            2013
            14 January 2013
            : 8
            : 1
            23341914 3544800 PONE-D-12-26955 10.1371/journal.pone.0052875

            This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Counts
            Pages: 15
            Funding
            This work was supported by grants from the Swedish Research Council (2008-743-57748-66, http://www.vr.se) and the European Commission as part of the Integrated project ‘Novel Testing Strategies for in vitro Assessment of Allergens; Sens-it-iv’ (LSHB-CT-2005-018681, http://www.sens-it-iv.eu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Categories
            Research Article
            Biology
            Genomics
            Genome Analysis Tools
            Transcriptomes
            Genome Expression Analysis
            Immunology
            Immune Cells
            Antigen-Presenting Cells
            Immunity
            Immune Activation
            Immune Tolerance
            Immunoregulation
            Immunotherapy
            Innate Immunity
            Immunologic Techniques
            Immunoassays
            Allergy and Hypersensitivity
            Antigen Processing and Recognition
            Immunomodulation

            Uncategorized

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