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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3723-3734. Prepublished online as a Blood First Edition Paper on August 11, 2008; DOI 10.1182/blood-2008-02-142091. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-142091v1 112/9/3723    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mancino, A. Articles by Sica, A. Search for Related Content PubMed PubMed Citation Articles by Mancino, A. Articles by Sica, A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Divergent effects of hypoxia on dendritic cell functions Alessandra Mancino1, Tiziana Schioppa2, Paola Larghi3, Fabio Pasqualini3, Manuela Nebuloni4, I-Hsuan Chen5, Silvano Sozzani6, Jonathan M. Austyn5, Alberto Mantovani1,7, and Antonio Sica3 1 Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy; 2 Cancer Research UK, Translational Oncology, John Vane Science Centre, London, United Kingdom; 3 Fondazione Humanitas per la Ricerca, Milan, Italy; 4 Institute of Pathology, Department of Clinical Sciences L. Sacco, University of Milan, Milan, Italy; 5 Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 6 Department of Biomedical Sciences and Biotechnology, Section of General Pathology and Immunology, University of Brescia, Brescia, Italy; and 7 University of Milan, Milan, Italy Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that patrol tissues to sense danger signals and activate specific immune responses. In addition, they also play a role in inflammation and tissue repair. Here, we show that oxygen availability is necessary to promote full monocyte-derived DC differentiation and maturation. Low oxygen tension (hypoxia) inhibits expression of several differentiation and maturation markers (CD1a, CD40, CD80, CD83, CD86, and MHC class II molecules) in response to lipopolysaccharide (LPS), as well as their stimulatory capacity for T-cell functions. These events are paralleled by impaired up-regulation of the chemokine receptor CCR7, an otherwise necessary event for the homing of mature DCs to lymph nodes. In contrast, hypoxia strongly up-regulates production of proinflammatory cytokines, particularly TNF and IL-1β, as well as the inflammatory chemokine receptor CCR5. Subcutaneous injection of hypoxic DCs into the footpads of mice results in defective DC homing to draining lymph nodes, but enhanced leukocyte recruitment at the site of injection. Thus, hypoxia uncouples the promotion of inflammatory and tissue repair from sentinel functions in DCs, which we suggest is a safeguard mechanism against immune reactivity to damaged tissues. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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