title: Finasteride Enhances the Generation of Human Myeloid-Derived Suppressor Cells by Up-Regulating the COX2/PGE2 Pathway.
abstract: Myeloid-derived suppressor cells (MDSCs) have been known to be a key factor in the regulation of the immune system under numerous conditions such as tumors, infections, autoimmune diseases, and transplantations. In contrast to the proposed deleterious role of MDSCs in tumors and infections, MDSCs with their suppressive function are now proved to have the beneficial potential of suppressing the autoimmune response and promoting tolerance to transplantation. Therefore, the expansion of MDSCs could be a promising therapeutic strategy for many diseases. In this study, we aimed to identify FDA-approved drugs that could aid in the expansion of functional MDSCs. We performed a high-throughput screening (HTS) of FDA-approved drugs based on the in vitro human MDSC-differentiation system and identified finasteride (FIN) to have the best potency to aid the generation of human MDSCs. The FIN-induced MDSCs were quite similar to monocytic MDSCs with regard to their surface phenotype, morphology, immunosuppressive function, and related gene expression. Next, we aimed to determine the mechanism of action of FIN and found that FIN induced the expansion of MDSCs through up-regulation of the COX2/PGE2 pathway by enhancing the activity of COX2 promoter. In addition, the administration of indomethacin (IND), a COX2 inhibitor, abrogated the effect of FIN. Based on these results, we suggested that FIN could find applications in the future in the expansion of MDSCs. Further development of FIN-like compounds could be a novel strategy for generating functional MDSCs for immunosuppressive therapies in various immune disorder conditions.
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Wu
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.|Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yingtong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.|Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.|Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.|Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.|Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Guangzhou Blood Center, Guangzhou, Guangdong, China.
authors.forename: Yongshui
authors.initials: Y
authors.lastname: Fu
mesh_terms: D015551:Autoimmunity / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D018120:Finasteride / Q000008:administration & dosage*; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D018120:Finasteride; D051546:Cyclooxygenase 2; D007213:Indomethacin