role of myeloid-derived suppressor cells in amelioration of experimental autoimmune hepatitis following activation of trpv1 receptors by cannabidiolmyeloid-derived抑制细胞的作用改善实验性自身免疫性肝炎后激活trpv1受体的大麻二酚.pdfVIP

Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol Venkatesh L. Hegde, Prakash S. Nagarkatti, Mitzi Nagarkatti* Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America Abstract Background: Myeloid-derived suppressor cells (MDSCs) are getting increased attention as one of the main regulatory cells of the immune system. They are induced at sites of inflammation and can potently suppress T cell functions. In the current study, we demonstrate how activation of TRPV1 vanilloid receptors can trigger MDSCs, which in turn, can inhibit inflammation and hepatitis. Methodology/Principal Findings: Polyclonal activation of T cells, following injection of concanavalin A (ConA), in C57BL/6 mice caused acute hepatitis, characterized by significant increase in aspartate transaminase (AST), induction of inflammatory cytokines, and infiltration of mononuclear cells in the liver, leading to severe liver injury. Administration of cannabidiol (CBD), a natural non-psychoactive cannabinoid, after ConA challenge, inhibited hepatitis in a dose-dependent manner, along with all of the associated inflammation markers. Phenotypic analysis of liver infiltrating cells showed that CBD- mediated suppression of hepatitis was associated with increased induction of arginase-expressing CD11b+Gr-1+ MDSCs. Purified CBD-induced MDSCs could effectively suppress T cell proliferation in vitro in arginase-dependent manner. ¨ Furthermore, adoptive transfer of purified MDSCs into naıve mice co