Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances protection against tumors and infections, but GM-CSF–deficient mice develop inflammatory disease. Here we show that GM-CSF is required for the expression of milk fat globule EGF 8 (MFG-E8) in antigen-presenting cells, and that MFG-E8–mediated uptake of apoptotic cells is a key determinant of GM-CSF–triggered tolerance and immunity. Upon exposure to apoptotic cells, GM-CSF–deficient antigen-presenting cells (APCs) produce an altered cytokine profile that results in decreased Tregs and increased Th1 cells, whereas concurrent ablation of IFN-γ promotes Th17 cells. In wild-type mice, MFG-E8 attenuates the vaccination activity of GM-CSF–secreting tumor cells through Treg induction, whereas a dominant-negative MFG-E8 mutant potentiates GM-CSF–stimulated tumor destruction through Treg inhibition. These findings clarify the immunoregulatory effects of apoptotic cells and suggest new therapeutic strategies to modulate CD4+ T cell subsets in cancer and autoimmunity.
Masahisa Jinushi, Yukoh Nakazaki, Michael Dougan, Daniel R. Carrasco, Martin Mihm, Glenn Dranoff
Usage data is cumulative from April 2023 through April 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 931 | 90 |
63 | 28 | |
Figure | 198 | 12 |
Supplemental data | 7 | 1 |
Citation downloads | 15 | 0 |
Totals | 1,214 | 131 |
Total Views | 1,345 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.