Comment[ArrayExpressAccession]	E-GEOD-50949
MAGE-TAB Version	1.1						
Public Release Date	2015-09-01
Investigation Title	MDSC exacerbate acute hepatitis, mature and loose suppressor function CD40 dependent						
Comment[Submitted Name]	MDSC exacerbate acute hepatitis, mature and loose suppressor function CD40 dependent
Experiment Description	Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that accumulate in blood, liver, spleen and tumors upon chronic inflammation and tumor development in patients and mice. Acute hepatitis is characterized by a fast infiltration of inflammatory cells in the liver and increased enzymatic activity at this organ that could lead into liver fibrosis and cirrhosis. We have studied the biology of hepatic MDSC in acute hepatitis. Unexpectedly, hepatic MDSC, which accumulate in the liver of mice bearing subcutaneous tumors, failed to suppress inflammatory responses upon Con A injection, but instead were responsible for exacerbating acute liver damage. Phenotypic, genetic and functional studies demonstrated rapid changes of hepatic MDSC from a suppressor phenotype into a pro-inflammatory subset as early as 3 hours after Con A injection. An increase in the expression of pro-inflammatory cytokines, costimulatory molecules such as CD80, CD86 and CD40 along with a loss of suppressor function was noticed in mice upon Con A treatment. These changes were CD40-dependent and not found in CD40-/- MDSC. Interestingly, CD40 ligation of human MDSC in vitro resulted in down-regulation of arginase I expression and suppressor function. Finally, blockade of ROS production in hepatic MDSC ameliorated hepatocyte damage suggesting that MDSC mediated toxicity was ROS dependent. We believe that these findings reflect how MDSC plasticity can be modulated to promote inflammation, opening a new path for therapies targeting innate suppressive cells in cancer patients. EL4 tumors were established in C57BL/6 mice, then mice were injected either with PBS (n=3) or 12.5mg/kg Con A (n=3). Three hours later mice were sacrificed, liver CD11b+Gr-1+ cells were sorted and samples were processed for gene expression analysis.						
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl					
Person Last Name	Marincola						
Person First Name	Francesco						
Person Mid Initials	Maria						
Person Email	fmarincola@sidra.org						
Person Affiliation	Sidra Medical and Research Center						
Person Phone	301-793-8210						
Person Address	Sidra Medical and Research Center, Al Nasr Tower, AL Corniche Street, PO Box 26999, Doha, Qatar						
Person Roles	submitter						
Protocol Name	P-GSE50949-1	P-GSE50949-4	P-GSE50949-5	P-GSE50949-7	P-GSE50949-2	P-GSE50949-3	P-GSE50949-6
Protocol Description	Affymetrix RMA Data Processing Calculation Method: After Robust Multichip Average (RMA) normalization, the statistically significant gene expression changes were functionally analyzed using Partek Genomic Suite 6.6 (St. Louis, MO). ID_REF = Affymetrix ID VALUE = RMA normalized signal intensity (Log2)	Affymetrix Terminal Labeling Kit Other: Affymetrix Terminal Labeling Kit according to manufacturer's protocol.	Affymetrix Hybrization Protocol Other: Terminally labeled cDNA were hybridized to the Mouse Gene 1.0 ST array (Affymetrix) according to the manufacturers' instructions.	Agent: Type IV Concanavalin A (Con A) Treatment dose: 12.5ug/kg Treatment time: 3 hours	Agent: PBS Treatment time: 3 hours	Sample Extraction Protocol Other: RNA extractions were performed using NucleoSpin RNA II (Macherey-Nagel) followed by whole transcriptome amplification using WT expression kit (Invitrogen).	Affymetrix Scanning Protocol Other: Arrays were then scanned on a GeneChip Scanner 3000 7G (Affymetrix).
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	sample treatment protocol	nucleic acid extraction protocol	array scanning protocol
Experimental Factor Name	other						
Experimental Factor Type	other						
Comment[SecondaryAccession]	GSE50949						
Comment[GEOReleaseDate]	2015-09-01						
Comment[ArrayExpressSubmissionDate]	2013-09-17						
Comment[GEOLastUpdateDate]	2015-09-01						
Comment[AEExperimentType]	transcription profiling by array						
SDRF File	E-GEOD-50949.sdrf.txt