title: Atorvastatin promotes the expansion of myeloid-derived suppressor cells and attenuates murine colitis.
abstract: Statins, widely prescribed as cholesterol-lowering drugs, have recently been extensively studied for their pleiotropic effects on immune systems, especially their beneficial effects on autoimmune and inflammatory disorders. However, the mechanism of statin-induced immunosuppression is far from understood. Here, we found that atorvastatin promoted the expansion of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Atorvastatin-derived MDSCs suppressed T-cell responses by nitric oxide production. Addition of mevalonate, a downstream metabolite of 3-hydroxy-3-methylglutaryl coenzyme A reductase, almost completely abrogated the effect of atorvastatin on MDSCs, indicating that the mevalonate pathway was involved. Along with the amelioration of dextran sodium sulphate (DSS) -induced murine acute and chronic colitis, we observed a higher MDSC level both in spleen and intestine tissue compared with that from DSS control mice. More importantly, transfer of atorvastatin-derived MDSCs attenuated DSS acute colitis and T-cell transfer of chronic colitis. Hence, our data suggest that the expansion of MDSCs induced by statins may exert a beneficial effect on autoimmune diseases. In summary, our study provides a novel potential mechanism for statins-based treatment in inflammatory bowel disease and perhaps other autoimmune diseases.
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Lei
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Shi
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yingjiao
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: He
authors.affiliation: Programme in Immunology, Affiliated Guangzhou Women and Children's Medical Centre, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. zhouj72@mail.sysu.edu.cn.|Institute of Human Virology, Sun Yat-sen University, Guangzhou, China. zhouj72@mail.sysu.edu.cn.|Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, China. zhouj72@mail.sysu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D006801:Humans; D007165:Immunosuppression Therapy; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D016264:Dextran Sulfate; D000069059:Atorvastatin; D008798:Mevalonic Acid
keywords: atorvastatin; immunosuppression; murine colitis; myeloid-derived suppressor cells; nitric oxide