PMID- 18725395 OWN - NLM STAT- MEDLINE DCOM- 20090122 LR - 20161124 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 84 IP - 6 DP - 2008 Dec TI - Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile. PG - 1472-82 LID - 10.1189/jlb.0208082 [doi] AB - 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. FAU - Elia, Angela Rita AU - Elia AR AD - Centre for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Torino, Italy. FAU - Cappello, Paola AU - Cappello P FAU - Puppo, Maura AU - Puppo M FAU - Fraone, Tiziana AU - Fraone T FAU - Vanni, Cristina AU - Vanni C FAU - Eva, Alessandra AU - Eva A FAU - Musso, Tiziana AU - Musso T FAU - Novelli, Francesco AU - Novelli F FAU - Varesio, Luigi AU - Varesio L FAU - Giovarelli, Mirella AU - Giovarelli M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080825 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Antigens) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (DNA-Binding Proteins) RN - 0 (ETV5 protein, human) RN - 0 (Transcription Factors) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) SB - IM MH - Antigens/*metabolism MH - Cell Differentiation/*physiology MH - Cell Movement MH - Cell Proliferation MH - Cells, Cultured MH - Chemokines/*metabolism MH - Cytokines/metabolism MH - DNA-Binding Proteins/metabolism MH - Dendritic Cells/*cytology/metabolism MH - Down-Regulation MH - Flow Cytometry MH - Humans MH - Hypoxia/*metabolism MH - Lymphocyte Activation MH - Macrophages/cytology/immunology/metabolism MH - Monocytes/cytology/immunology/metabolism MH - Phenotype MH - Phosphorylation MH - T-Lymphocytes/immunology/metabolism MH - Transcription Factors/metabolism MH - rho GTP-Binding Proteins/metabolism EDAT- 2008/08/30 09:00 MHDA- 2009/01/23 09:00 CRDT- 2008/08/30 09:00 PHST- 2008/08/30 09:00 [pubmed] PHST- 2009/01/23 09:00 [medline] PHST- 2008/08/30 09:00 [entrez] AID - jlb.0208082 [pii] AID - 10.1189/jlb.0208082 [doi] PST - ppublish SO - J Leukoc Biol. 2008 Dec;84(6):1472-82. doi: 10.1189/jlb.0208082. Epub 2008 Aug 25.