First Author | Hegde VL | Year | 2010 |
Journal | Eur J Immunol | Volume | 40 |
Issue | 12 | Pages | 3358-71 |
PubMed ID | 21110319 | Mgi Jnum | J:174663 |
Mgi Id | MGI:5140294 | Doi | 10.1002/eji.201040667 |
Citation | Hegde VL, et al. (2010) Cannabinoid receptor activation leads to massive mobilization of myeloid-derived suppressor cells with potent immunosuppressive properties. Eur J Immunol 40(12):3358-71 |
abstractText | Cannabinoid receptor activation by agents such as Delta(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 CSF. Moreover, administration of anti-granulocyte CSF Ab 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 the periphery with a corresponding decrease in the proportion of CD11b(+)Gr-1(+) cells in the bone marrow, as well as in vivo BrdU labeling and cell-cycle analysis, showed that THC induced mobilization of these cells from bone marrow and their expansion in the periphery. Use of selective antagonists SR141716A and SR144528 against cannabinoid receptors 1 and 2, respectively, as well as receptor-deficient mice showed that induction of MDSC was mediated through activation of both cannabinoid receptors 1 and 2. These studies demonstrate that cannabinoid receptor signaling may play a crucial role in immune regulation via the induction of MDSC. |