Treating Autoimmune Diseases by Targeting IL-23 with Gene-Silencing Pyrrole-Imidazole Polyamide.
J Immunol
; 204(8): 2053-2063, 2020 04 15.
Article
em En
| MEDLINE
| ID: mdl-32169850
ABSTRACT
Autoimmune diseases are a physiological state that immune responses are directed against and damage the body's own tissues. Numerous studies have demonstrated promising therapeutic effects in certain autoimmune diseases by targeting IL-23/IL-17 axis, mostly through using Abs against IL-23 or IL-17A. Pyrrole-imidazole polyamides are nuclease-resistant compounds that inhibit gene expression through binding to the minor groove of DNA. To develop a novel gene-silencing agent that targets IL-23/IL-17 axis, we designed polyamide that specifically binds to the transcription factor c-Rel-binding site located in the promoter of IL-23p19 subunit. Our study showed that this polyamide is capable of entering into nucleus with high efficiency in dendritic cells and macrophage. In addition, it prevented the binding of c-Rel to the promoter of IL-23p19 in vivo and specifically inhibited the expression of IL-23. More importantly, we demonstrated that this polyamide is therapeutically effective using both the imiquimod-induced psoriasis and experimental autoimmune uveitis mouse models. Taken together, these results indicate that pyrrole-imidazole polyamide targeting IL-23p19 could be a novel and feasible therapeutic strategy for patients with autoimmune diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
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Inativação Gênica
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Subunidade p19 da Interleucina-23
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Nylons
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article