title: Treating psoriasis by targeting its susceptibility gene Rel.
abstract: Psoriasis is a chronic inflammatory disorder of the skin. Accumulating evidence indicates that the Rel gene, a member of the NF-κB family, is a risk factor for the disease. We sought to investigate whether psoriasis can be prevented by directly targeting the Rel gene transcript, i.e., the c-Rel mRNA. Using chemically-modified c-Rel specific siRNA (siRel) and poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) micelles, we successfully knocked down the expression of c-Rel, and showed that the expression of cytokine IL-23, a direct target of c-Rel that can drive the development of IL-17-producing T cells, was markedly inhibited. More importantly, treating mice with siRel not only prevented but also ameliorated imiquimod (IMQ)-induced psoriasis. Mechanistic studies showed that siRel treatment down-regulated the expression of multiple inflammatory cytokines. Taken together, these results indicate that the susceptibility gene Rel can be targeted to treat and prevent psoriasis.
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Fan
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Linjiang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Huqiang
authors.initials: H
authors.lastname: Yi
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Liu
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Geng
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wan
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pathology and Laboratory of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States.
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Shenzhen Laboratory of Fully Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China. Electronic address: qg.ruan@siat.ac.cn.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Ruan
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D020573:Genes, rel / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D034743:RNA-Induced Silencing Complex / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex
keywords: IL-17A; PEG-PLL-PLLeu micelles; Psoriasis; c-Rel; siRNA