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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 (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 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 Mancino, A. Articles by Sica, A. Search for Related Content PubMed PubMed Citation Articles by Mancino, A. Articles by Sica, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 29, 2008 Accepted June 30, 2008 Divergent effects of hypoxia on dendritic cell functions Alessandra Mancino, Tiziana Schioppa, Paola Larghi, Fabio Pasqualini, Manuela Nebuloni, I-Hsuan Chen, Silvano Sozzani, Jonathan M Austyn, Alberto Mantovani, and Antonio Sica* Department of Inflammation and Immunology, Istituto Clinico Humanitas, IRCCS, 20089 Rozzano, Milan, Italy, Rozzano (Milan), Italy Translational Oncology, John Vane Science Centre, Cancer Research UK, London, United Kingdom Department of Inflammation and Immunology, Fondazione Humanitas per la Ricerca, Rozzano (Milan), Italy Institute of Pathology, Department of Clinical Sciences, L. Sacco, University, Milan, Italy Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom Department of Biomedical Sciences and Biotechnology, Section of General Pathology and Immunology, University of Brescia, Brescia, Italy University of Milan, Rozzano (Milan), Italy * Corresponding author; email: antonio.sica{at}humanitas.it. Dendritic cells (DC) are professional antigen-presenting cells (APC) 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 DC to lymph nodes. In contrast, hypoxia strongly up-regulates production of pro-inflammatory cytokines, particularly TNF and IL-1, as well as the inflammatory chemokine receptor CCR5. Subcutaneous injection of hypoxic DC 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 DC, which we suggest is a safeguard mechanism against immune reactivity to damaged tissues. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Sorio and P. Melotti Editorial: The role of macrophages and their scavenger receptors in cystic fibrosis J. Leukoc. Biol., September 1, 2009; 86(3): 465 - 468. [Full Text] [PDF]

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