title: Directed evolution of a soluble human IL-17A receptor for the inhibition of psoriasis plaque formation in a mouse model.
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.
authors: Department of Life Sciences, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
authors: Marianna
authors: M
authors: Zaretsky
authors: Revital
authors: R
authors: Etzyoni
authors: Joel
authors: J
authors: Kaye
authors: Liora
authors: L
authors: Sklair-Tavron
authors: Amir
authors: A
authors: Aharoni
mesh_terms: D000818:Animals; D019020:Directed Molecular Evolution; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D055550:Protein Stability; D011565:Psoriasis / Q000188:drug therapy*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins