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

Angela Rita Elia, Paola Cappello, Maura Puppo, Tiziana Fraone, Cristina Vanni, Alessandra Eva, Tiziana Musso, Francesco Novelli, Luigi Varesio, Mirella Giovarelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1472-1482
Number of pages11
JournalJournal of Leukocyte Biology
Volume84
Issue number6
DOIs
Publication statusPublished - Dec 1 2008

Keywords

  • Antigen-presenting cells
  • Chemokine receptors
  • Cytokines
  • Phagocytosis/endocytosis
  • T cell activation

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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