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Human dendritic cells differentiated in hypoxia down‐modulate antigen uptake and change their chemokine expression profile
Author(s) -
Elia Angela Rita,
Cappello Paola,
Puppo Maura,
Fraone Tiziana,
Vanni Cristina,
Eva Alessandra,
Musso Tiziana,
Novelli Francesco,
Varesio Luigi,
Giovarelli Mirella
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0208082
Subject(s) - ccl20 , microbiology and biotechnology , biology , chemokine , cxcl1 , ccl2 , immunology , antigen , immune system , dendritic cell , cxcl10 , chemokine receptor
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.