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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1590-1597. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-06-2332. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 2004-06-2332v1 105/4/1590    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Noronha, S. Articles by Thrasher, A. J. Search for Related Content PubMed PubMed Citation Articles by de Noronha, S. Articles by Thrasher, A. J. Related Collections Immunobiology Cell Adhesion and Motility Cytoskeleton Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein Sofia de Noronha, Samantha Hardy, Joanna Sinclair, Michael P. Blundell, Jessica Strid, Oliver Schulz, Jörg Zwirner, Gareth E. Jones, David R. Katz, Christine Kinnon, and Adrian J. Thrasher From the Molecular Immunology Unit, Institute of Child Health, London, United Kingdom; the Immunobiology Unit, Institute of Child Health, London, United Kingdom; the Immunobiology Laboratory, Cancer Research United Kingdom, Lincoln's Inn Fields Laboratories, London, United Kingdom; the Department of Immunology, Georg-August-University Göttingen, Germany; the Randall Centre for Molecular Mechanisms of Cell Function, King's College London, United Kingdom; the Department of Immunology, University College London, Windeyer Institute, United Kingdom; and the Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, United Kingdom. Regulated migration and spatial localization of dendritic cells (DCs) are critical events during the initiation of physiologic immune responses and maintenance of tolerance. Here we have used cells deficient in the Wiskott-Aldrich syndrome protein (WASp) to demonstrate the importance of dynamic remodeling of the actin cytoskeleton for these trafficking processes to occur in vitro and in vivo. On fibronectin-coated surfaces, WASp-null immature murine DCs exhibited defects both of attachment and detachment, resulting in impaired net translocation compared with normal cells. The chemokinetic response to CCL21, which is critical for normal lymphatic trafficking, was also abrogated in the absence of WASp. In vivo in both fluorescein isothiocyanate (FITC) and oxazolone contact hypersensitivity models, WASp-null Langerhans cell (LC) migration was compromised, as judged by exit from the skin as well as by homing to the draining lymph node (LN). Furthermore, following systemic challenge with lipopolysaccharide (LPS) or toxoplasma-derived antigen, WASp-null DCs showed incomplete redistribution to T-cell areas in the spleen. Instead, they were retained ectopically in the marginal zone. DC trafficking in vivo is therefore dependent on a normally regulated actin cytoskeleton, which performs an essential function during maintenance of physiologic immunity and when disturbed may contribute significantly to the immunopathology of Wiskott-Aldrich Syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Pulecio, E. Tagliani, A. Scholer, F. Prete, L. Fetler, O. R. Burrone, and F. Benvenuti Expression of Wiskott-Aldrich Syndrome Protein in Dendritic Cells Regulates Synapse Formation and Activation of Naive CD8+ T Cells J. Immunol., July 15, 2008; 181(2): 1135 - 1142. [Abstract] [Full Text] [PDF] G. Bouma, S. Burns, and A. J. Thrasher Impaired T-cell priming in vivo resulting from dysfunction of WASp-deficient dendritic cells Blood, December 15, 2007; 110(13): 4278 - 4284. [Abstract] [Full Text] [PDF] M. H. Maillard, V. Cotta-de-Almeida, F. Takeshima, D. D. Nguyen, P. Michetti, C. Nagler, A. K. Bhan, and S. B. Snapper The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells J. Exp. Med., February 19, 2007; 204(2): 381 - 391. [Abstract] [Full Text] [PDF] S. Sabri, A. Foudi, S. Boukour, B. Franc, S. Charrier, M. Jandrot-Perrus, R. W. Farndale, A. Jalil, M. P. Blundell, E. M. Cramer, et al. Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment Blood, July 1, 2006; 108(1): 134 - 140. [Abstract] [Full Text] [PDF]

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