Cannabinoid receptor activation leads to massive mobilization of myeloid-derived suppressor cells with potent immunosuppressive properties

Summary—Cannabinoid receptor activation by agents such as Δ 9 -tetrahydrocannabinol (THC) is known to trigger immune suppression. Here, we show that administration of THC in mice leads to rapid and massive expansion of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) expressing functional arginase and exhibiting potent immunosuppressive properties both in vitro and in vivo. The induction of MDSC by THC was associated with a significant increase in granulocyte colony-stimulating factor (G-CSF). Moreover, administration of anti-G-CSF antibody inhibited the induction of MDSC by THC. THC was able to induce MDSC in TLR4 mutant C3H and C57BL10/ScN mice and hence acted independently of TLR4. Accumulation of MDSC in...