PMID- 21148811 OWN - NLM STAT- MEDLINE DCOM- 20110509 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 117 IP - 9 DP - 2011 Mar 3 TI - Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo. PG - 2625-39 LID - 10.1182/blood-2010-06-292136 [doi] AB - Dendritic cells (DCs) are a heterogeneous group of professional antigen-presenting cells functioning as sentinels of the immune system and playing a key role in the initiation and amplification of innate and adaptive immune responses. DC development and functions are acquired during a complex differentiation and maturation process influenced by several factors present in the local milieu. A common feature at pathologic sites is represented by hypoxia, a condition of low pO(2), which creates a unique microenvironment affecting cell phenotype and behavior. Little is known about the impact of hypoxia on the generation of mature DCs (mDCs). In this study, we identified by gene expression profiling a significant cluster of genes coding for immune-related cell surface receptors strongly up-regulated by hypoxia in monocyte-derived mDCs and characterized one of such receptors, TREM-1, as a new hypoxia-inducible gene in mDCs. TREM-1 associated with DAP12 in hypoxic mDCs, and its engagement elicited DAP12-linked signaling, resulting in ERK-1, Akt, and IkappaBalpha phosphorylation and proinflammatory cytokine and chemokine secretion. Finally, we provided the first evidence that TREM-1 is expressed on mDCs infiltrating the inflamed hypoxic joints of children affected by juvenile idiopathic arthritis, representing a new in vivo marker of hypoxic mDCs endowed with proinflammatory properties. CI - (c) 2011 by The American Society of Hematology FAU - Bosco, Maria Carla AU - Bosco MC AD - Laboratory of Molecular Biology, G. Gaslini Institute, Genova, Italy. mariacarlabosco@ospedalegaslini.ge.it FAU - Pierobon, Daniele AU - Pierobon D FAU - Blengio, Fabiola AU - Blengio F FAU - Raggi, Federica AU - Raggi F FAU - Vanni, Cristina AU - Vanni C FAU - Gattorno, Marco AU - Gattorno M FAU - Eva, Alessandra AU - Eva A FAU - Novelli, Francesco AU - Novelli F FAU - Cappello, Paola AU - Cappello P FAU - Giovarelli, Mirella AU - Giovarelli M FAU - Varesio, Luigi AU - Varesio L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101210 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Biomarkers) RN - 0 (Chemokines) RN - 0 (Cross-Linking Reagents) RN - 0 (Inflammation Mediators) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Immunologic) RN - 0 (TREM1 protein, human) RN - 0 (TYROBP protein, human) RN - 0 (Triggering Receptor Expressed on Myeloid Cells-1) RN - S88TT14065 (Oxygen) SB - IM CIN - Blood. 2011 Mar 3;117(9):2561-2. PMID: 21372159 MH - Adaptor Proteins, Signal Transducing/metabolism MH - Arthritis, Juvenile/genetics/pathology MH - Biomarkers/metabolism MH - Cell Differentiation/drug effects/*genetics MH - Cell Hypoxia/drug effects/genetics MH - Chemokines/metabolism MH - Cross-Linking Reagents/pharmacology MH - Data Mining MH - Dendritic Cells/*cytology/drug effects/*metabolism MH - *Gene Expression Profiling MH - Gene Expression Regulation/drug effects MH - Humans MH - Inflammation Mediators/metabolism MH - Membrane Glycoproteins/genetics/*metabolism MH - Membrane Proteins/metabolism MH - Monocytes/cytology MH - Oxygen/pharmacology MH - Phenotype MH - Receptors, Immunologic/*genetics/metabolism MH - Signal Transduction/drug effects/genetics MH - Synovial Fluid/drug effects/metabolism MH - Triggering Receptor Expressed on Myeloid Cells-1 EDAT- 2010/12/15 06:00 MHDA- 2011/05/10 06:00 CRDT- 2010/12/15 06:00 PHST- 2010/12/15 06:00 [entrez] PHST- 2010/12/15 06:00 [pubmed] PHST- 2011/05/10 06:00 [medline] AID - S0006-4971(20)39059-5 [pii] AID - 10.1182/blood-2010-06-292136 [doi] PST - ppublish SO - Blood. 2011 Mar 3;117(9):2625-39. doi: 10.1182/blood-2010-06-292136. Epub 2010 Dec 10.