Directed evolution of a soluble human IL-17A receptor for the inhibition of psoriasis plaque formation in a mouse model

Marianna Zaretsky, Revital Etzyoni, Joel Kaye, Liora Sklair-Tavron, Amir Aharoni

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Interleukin-17 (IL-17) is a T-cell-derived cytokine that promotes inflammatory pathology in autoimmune diseases. Blocking IL-17A interactions with its endogenous IL-17 receptor (IL-17RA) can constitute an important target for therapeutic intervention. Here, we utilized a directed evolution approach to generate soluble IL-17RA mutants that exhibit increased IL-17A binding affinity and thermostability, relative to the wild-type. Human fibroblast cell-based assay and in vivo analysis in mice indicated that two improved IL-17RA mutants efficiently inhibit the secretion of IL-17A-induced proinflammatory cytokines. Analysis of one of these mutants in a psoriasis mouse model showed its efficacy in promoting the recovery of psoriasis plaques. This mutant can be used as a promising drug candidate for the treatment of psoriasis and may be a therapeutic agent for various other autoimmune diseases.

Original languageEnglish
Pages (from-to)202-211
Number of pages10
JournalChemistry and Biology
Volume20
Issue number2
DOIs
StatePublished - 21 Feb 2013

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