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In this study, we observed that administering CBD into naive mice triggers robust induction of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) in the peritoneum, which expressed functional arginase 1, and potently suppressed T cell proliferation ex vivo. Furthermore, CBD-MDSC suppressed LPS-induced acute inflammatory response upon adoptive transfer in vivo. CBD-induced suppressor cells were comprised of CD11b+Ly6-G+Ly6-C+ granulocytic and CD11b+Ly6-G\u2212Ly6-C+ monocytic subtypes, with monocytic MDSC exhibiting higher T cell\u2013suppressive function. Induction of MDSC by CBD was markedly attenuated in Kit-mutant (KitW\/W-v) mast cell\u2013deficient mice. MDSC response was reconstituted upon transfer of wild-type bone marrow\u2013derived mast cells in KitW\/W-v mice, suggesting the key role of cKit (CD117) as well as mast cells. Moreover, mast cell activator compound 48\/80 induced significant levels of MDSC in vivo. CBD administration in mice induced G-CSF, CXCL1, and M-CSF, but not GM-CSF. G-CSF was found to play a key role in MDSC mobilization inasmuch as neutralizing G-CSF caused a significant decrease in MDSC. Lastly, CBD enhanced the transcriptional activity of peroxisome proliferator-activated receptor \u03b3 in luciferase reporter assay, and PPAR-\u03b3 selective antagonist completely inhibited MDSC induction in vivo, suggesting its critical role. Together, the results suggest that CBD may induce activation of PPAR-\u03b3 in mast cells leading to secretion of G-CSF and consequent MDSC mobilization. CBD being a major component of Cannabis, our study indicates that marijuana may modulate or dysregulate the immune system by mobilizing MDSC.<\/jats:p>","DOI":"10.4049\/jimmunol.1401844","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T01:41:13Z","timestamp":1430185273000},"page":"5211-5222","source":"Crossref","is-referenced-by-count":79,"title":["Critical Role of Mast Cells and Peroxisome Proliferator\u2013Activated Receptor \u03b3 in the Induction of Myeloid-Derived Suppressor Cells by Marijuana Cannabidiol In Vivo"],"prefix":"10.1093","volume":"194","author":[{"given":"Venkatesh L","family":"Hegde","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, SC 29209"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udai P","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, SC 29209"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash S","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, SC 29209"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitzi","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, SC 29209"},{"name":"Wm. 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