Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function.

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

SUBMITTER: Sander LE 

PROVIDER: S-EPMC2901069 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature