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

Venkatesh L. Hegde, Mitzi Nagarkatti, Prakash S. Nagarkatti

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Cannabinoid receptor activation by agents such as δ9-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.

Original languageEnglish (US)
Pages (from-to)3358-3371
Number of pages14
JournalEuropean Journal of Immunology
Volume40
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Arginase
  • Cannabinoid receptors
  • Granulocyte CSF
  • Immune suppression
  • Myeloid-derived suppressor cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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