Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile.
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.
Elia
Angela Rita
AR
Centre for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Torino, Italy.
Cappello
Paola
P
Puppo
Maura
M
Fraone
Tiziana
T
Vanni
Cristina
C
Eva
Alessandra
A
Musso
Tiziana
T
Novelli
Francesco
F
Varesio
Luigi
L
Giovarelli
Mirella
M
D000941:Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000941:Antigens; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins