Figure 9. Proposed model of the dual roles for GM-CSF in tolerance and protective immunity.

Top: GM-CSF is required for the expression of MFG-E8 in antigen-presenting cells. Upon exposure of phosphatidylserine (PS) on the surface of apoptotic cells, MFG-E8 promotes their engulfment by antigen-presenting cells, which results in the stimulations of Tregs. Bottom: In the setting of stress, TLR agonists and necrotic cells downregulate MFG-E8 on antigen-presenting cells, whereby GM-CSF promotes CD4⁺ effector T cell responses.