Treatment of il-17 mediated disease by blocking sefir-sefir interactions

Abstract

A method of treating an IL-17 mediated disease in a subject by administering to the subject a therapeutically effective amount of a of a cell-permeable decoy peptide that competitively inhibits binding of the SEFIR domain of IL-17R to the SEFIR domain of Act1. In particular, it has been determined that the αC helix region of the SEFIR domain of both IL-17R and Act1 plays an important role in the association of IL-17R and Act1. To facilitate cell permeation, the decoy peptide is preferably conjugated to a protein transduction domain. Examples of IL-17 mediated diseases include various human and animal inflammatory and autoimmune diseases such as asthma.

What is claimed is: 
     
         1 . A method of treating an interleukin-17 (IL-17) mediated disease in a subject, comprising administering to the subject a therapeutically effective amount of a cell-permeable decoy peptide that competitively inhibits binding of the SEFIR domain of IL-17R to the SEFIR domain of Act1. 
     
     
         2 . The method of  claim 1 , wherein the decoy peptide consists of less than about 50 amino acids. 
     
     
         3 . The method of  claim 1 , wherein the decoy peptide comprises an amino acid sequence substantially homologous to at least a portion of the amino acid sequence of the αC helix region of the SEFIR domain of Act1 or at least a portion of the αC helix region of the SEFIR domain of IL-17R. 
     
     
         4 . The method of  claim 1 , wherein the decoy peptide comprises an amino acid sequence substantially homologous to at least a portion of the amino acid sequence of the αC helix region of the SEFIR domain of Act1. 
     
     
         5 - 7 . (canceled) 
     
     
         8 . The method of  claim 4 , wherein the decoy peptide further comprises a protein transduction domain. 
     
     
         9 . The method of  claim 8 , wherein the protein transduction domain is derived from antennapedia. 
     
     
         10 . The method of  claim 9 , wherein the protein transduction domain has the amino acid sequence DRQIKIWFQNRRMKWKK (SEQ ID NO: 11). 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the decoy peptide comprises an amino acid sequence substantially homologous to at least a portion of the amino acid sequence of the αC helix region of the SEFIR domain of IL-17R. 
     
     
         13 . The method of  claim 12 , wherein the decoy peptide comprises the amino acid sequence DLFXXA (SEQ ID NO: 2). 
     
     
         14 . The method of  claim 12 , wherein the decoy peptide comprises the amino acid sequence QDLFPLA (SEQ ID NO: 6) or GDLFTAA (SEQ ID NO: 7). 
     
     
         15 . The method of  claim 12 , wherein the decoy peptide further comprises a protein transduction domain. 
     
     
         16 . The method of  claim 15 , wherein the protein transduction domain is derived from antennapedia. 
     
     
         17 . The method of  claim 16 , wherein the protein transduction domain has the amino acid sequence DRQIKIWFQNRRMKWKK (SEQ ID NO: 11). 
     
     
         18 . The method of  claim 1 , wherein the IL-17 mediated disease is an inflammatory disease or an autoimmune disease. 
     
     
         19 . The method of  claim 18 , wherein the IL-17 mediated disease is an inflammatory disease selected from the group consisting of asthma, inflammatory bowel disease, multiple sclerosis, experimental autoimmune encephalomyelitis, and allergen-induced pulmonary inflammation. 
     
     
         20 . The method of  claim 19 , wherein the disease is asthma. 
     
     
         21 . The method of  claim 18 , wherein the IL-17 mediated disease is an autoimmune disease selected from the group consisting of systemic lupus erythematosus, rheumatoid arthritis, allograft rejection, drug-induced lupus and psoriasis. 
     
     
         22 . The method of  claim 1 , wherein the IL-17 is IL-17A. 
     
     
         23 . The method of  claim 1 , wherein the IL-17 is IL-17E. 
     
     
         24 .- 31 . (canceled) 
     
     
         32 . An decoy peptide comprising an isolated peptide comprising an amino acid sequence substantially homologous to at least a portion of the amino acid sequence of the αC helix region of the SEFIR domain of IL-17R and comprising the amino acid sequence DLFXXA (SEQ ID NO: 2). 
     
     
         33 . The decoy peptide of  claim 32 , wherein the decoy peptide consists of less than about 50 amino acids. 
     
     
         34 . The decoy peptide of  claim 32 , wherein the decoy peptide comprises the amino acid sequence QDLFPLA (SEQ ID NO: 6) or GDLFTAA (SEQ ID NO: 7). 
     
     
         35 . The decoy peptide of  claim 32 , wherein the decoy peptide further comprises a protein transduction domain. 
     
     
         36 . The decoy peptide of  claim 35 , wherein the protein transduction domain is derived from antennapedia. 
     
     
         37 . The decoy peptide of  claim 35 , wherein the protein transduction domain has the amino acid sequence DRQIKIWFQNRRMKWKK (SEQ ID NO: 11).