Treating psoriasis by targeting its susceptibility gene Rel.

Tingting Fan, Shaowen Wang, Linjiang Yu, Huqiang Yi, Ruiling Liu, Wenwen Geng, Xiaochun Wan, Yifan Ma, Lintao Cai, Youhai H Chen, Qingguo Ruan

Clinical immunology (Orlando, Fla.) 2016 Apr

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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. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

Tingting Fan, Shaowen Wang, Linjiang Yu, Huqiang Yi, Ruiling Liu, Wenwen Geng, Xiaochun Wan, Yifan Ma, Lintao Cai, Youhai H Chen, Qingguo Ruan. Treating psoriasis by targeting its susceptibility gene Rel. Clinical immunology (Orlando, Fla.). 2016 Apr;165:47-54