The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in immunity and tumor development has remained unclear: mice deficient in GM-CSF have been shown to be sensitive to bacterial infection and prone to tumors, yet the persistent expression of GM-CSF has been shown to cause tumor cell invasion and spread to other locations. In a study appearing online in advance of publication in the July print issue of the Journal of Clinical Investigation, Glenn Dranoff and colleagues from Dana-Farber Cancer Institute explored the mechanisms underlying the physiological as well as pathophysiological effects of GM-CSF.
One mechanism by which GM-CSF promotes immune tolerance is by modulating the ability of macrophages to clear apoptotic cells, which leads to the production of immune suppressing cytokines. In the current study, the authors show that GM-CSF-mediated uptake of apoptotic cells by antigen-presenting cells (APCs) is itself mediated by the expression of milk fat globule EGF 8 (MFG-E8) on APCs. This uptake also triggers the production of regulatory T cells and Th1 cells that are critical to the regulation of the host immune response to tumors. The data demonstrate how GM-CFS-induced MFG-E8 expression mediates immune tolerance, which has potentially significant implications for cancer immunotherapy.
TITLE: MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and anti-inflammatory activities of GM-CSF
AUTHOR CONTACT:
Glenn Dranoff
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
JCI table of contents: June 7, 2007
Contact: Brooke Grindlinger
Journal of Clinical Investigation
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