E-GEOD-22009
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA127473
PROVIDER: E-GEOD-22009 | ExpressionAtlas | 2015-09-15
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-22009-analysis-methods.tsv | Tabular | |||
| E-GEOD-22009-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-22009-configuration.xml | Xml | |||
| E-GEOD-22009-percentile-ranks.tsv | Tabular | |||
| E-GEOD-22009.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 65 |
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Project description:Hepatic acute phase proteins control innate immune responses during infection by promoting myeloid derived suppressor cell function
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Project description:Acute phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and anti-inflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a murine model for polymicrobial sepsis we show here that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6-family cytokines, dramatically increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through signal transducer and activator of transcription (Stat)3 was required to control systemic inflammation. Notably, hepatic gp130/Stat3 activation was also a prerequisite to facilitate mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for anti-inflammatory properties in cancer. We show that MDSCs were critical to regulate innate inflammation and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. We identified serum amyloid A and Cxcl-1/KC as hepatic acute phase genes that cooperatively promoted MDSC mobilization, accumulation and survival. Administration of these proteins efficiently elevated MDSC numbers and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through acute phase proteins critically controls inflammatory responses during infection. Control [gp130f/f] and liver-specific Gp130 knockout [gp130delta(hepa)] mice were subjected to polymicrobial sepsis. Twelve hours after induction of sepsis mice were sacrificed and livers were removed. For control treatment mice were sacrified without any prior treatment. Total RNA was isolated and subjected to gene expression profiling.
2010-06-08 | E-GEOD-22009 | biostudies-arrayexpress
Project description:Acute phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and anti-inflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a murine model for polymicrobial sepsis we show here that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6-family cytokines, dramatically increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through signal transducer and activator of transcription (Stat)3 was required to control systemic inflammation. Notably, hepatic gp130/Stat3 activation was also a prerequisite to facilitate mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for anti-inflammatory properties in cancer. We show that MDSCs were critical to regulate innate inflammation and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. We identified serum amyloid A and Cxcl-1/KC as hepatic acute phase genes that cooperatively promoted MDSC mobilization, accumulation and survival. Administration of these proteins efficiently elevated MDSC numbers and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through acute phase proteins critically controls inflammatory responses during infection.
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Project description:Understanding the molecular mechanisms that initiate and control immunosuppression by myeloid cells is essential to overcoming the myeloid-induced disbalance of the immune system observed in patients. Myeloid cells are implicated in aggravated suppression of immunity as seen in cancer as well as in defective modulation of immune responses as observed in autoimmunity. Therefore, signaling pathways controlling immunomodulation by myeloid cells are an attractive target to potentially restore immune homeostasis and increase clinical benefit for a large number of patients. Here, we used label-free quantitative proteomics to identify proteins that are differentially expressed between different myeloid cells (myeloid-derived suppressor cells (MDSCs), tolerogenic dendritic cells (TolDCs), monocyte-derived dendritic cells (MoDCs) and precursor monocytes.
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