Accuri C6 Flow Cytometer System
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0208082

Received for publication February 4, 2008.
Revised July 16, 2008.
Accepted for publication August 5, 2008.

Article

Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile

Angela Rita Elia *{dagger}, Paola Cappello *{dagger}, Maura Puppo {ddagger}, Tiziana Fraone *{dagger}, Cristina Vanni {ddagger}, Alessandra Eva {ddagger}, Tiziana Musso {sect}, Francesco Novelli *{dagger}, Luigi Varesio {ddagger}, and Mirella Giovarelli *{dagger}@

*Center for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Torino, Italy; {dagger}Department of Medicine and Experimental Oncology, University of Torino, Torino, Italy; {ddagger}Laboratory of Molecular Biology, G. Gaslini Institute, Genova, Italy; and {sect}Department of Public Health and Microbiology, University of Torino, Torino Italy

@ To whom correspondence should be addressed. E-mail: mirella.giovarelli{at}unito.it.


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Abstract

Dendritic cells (DCs) are the most potent antigen-presenting cells and fine-tune the immune response. We have investigated hypoxia’s effects on the differentiation and maturation of DCs from human monocytes in vitro, and have shown that it affects DC functions. Hypoxic immature DCs (H-iDCs) significantly fail to capture antigens through down-modulation of the RhoA/Ezrin-Radixin-Moesin pathway and the expression of CD206. Moreover, H-iDCs released higher levels of CXCL1, VEGF, CCL20, CXCL8, and CXCL10 but decreased levels of CCL2 and CCL18, which predict a different ability to recruit neutrophils rather than monocytes and create a proinflammatory and proangiogenic environment. By contrast, hypoxia has no effect on DC maturation. Hypoxic mature DCs display a mature phenotype and activate both allogeneic and specific T cells like normoxic mDCs. This study provides the first demonstration that hypoxia inhibits antigen uptake by DCs and profoundly changes the DC chemokine expression profile and may have a critical role in DC differentiation, adaptation, and activation in inflamed tissues.

Key Words: antigen-presenting cells • phagocytosis/endocytosis • cytokines • T cell activation • chemokine receptors




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