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Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function
- Source :
- The Journal of Experimental Medicine, Journal of Experimental Medicine, 207(7), 1453-1464, Journal of Experimental Medicine 207 (2010) 7
- Publication Year :
- 2010
- Publisher :
- Rockefeller University Press, 2010.
-
Abstract
- 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 antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through STAT3 was required to control systemic inflammation. Notably, hepatic gp130–STAT3 activation was also essential for mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for antiinflammatory properties in cancer. MDSCs were critical to regulate innate inflammation, and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. The hepatic APPs serum amyloid A and Cxcl1/KC cooperatively promoted MDSC mobilization, accumulation, and survival, and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through APPs controls inflammatory responses during infection.
- Subjects :
- Male
Chemokine CXCL1
Apoptosis
Systemic inflammation
Voeding, Metabolisme en Genomica
Cell Movement
Cytokine Receptor gp130
Immunology and Allergy
Myeloid Cells
mechanisms
education.field_of_study
CD11b Antigen
Acute-phase protein
Metabolism and Genomics
CXCL1
liver-injury
Liver
Metabolisme en Genomica
Nutrition, Metabolism and Genomics
medicine.symptom
Signal Transduction
STAT3 Transcription Factor
mice
Immunology
Population
Inflammation
Biology
serum-amyloid-a
Article
signal transducer
gp130
Voeding
Sepsis
medicine
Animals
Serum amyloid A
education
VLAG
Nutrition
Serum Amyloid A Protein
Innate immune system
Bacteria
pathway
Gene Expression Profiling
Immunity, Innate
severe sepsis
inflammation
Hepatocytes
Myeloid-derived Suppressor Cell
activation
Spleen
Acute-Phase Proteins
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 207
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....f25abd2d39771e6b84ab90a421914991