Therapeutic application of isolated naturally-occurring soluble truncated forms of il-23 receptor

Abstract

The present invention relates to an isolated naturally-occurring soluble truncated IL-23Rα protein, which is a translated protein resulting from a mRNA splice variant of IL-23Rα. The soluble IL-23Rα proteins (e.g., Δ9 and Δ8,9) represents a novel soluble IL-23Rα protein, which is lacking a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end (due to frame-shift). ELISA reveals that Δ9 is present in blood and can serve as a diagnostic tool for auto-immune diseases including Crohn's disease. There is also provided a method of recombinant production for this soluble truncated form of IL-23Rα protein. More importantly, the present invention provides an utility application of the Δ9 and Δ8,9 protein in inhibit IL-23R-mediated cell signaling. More particularly, Δ9 and Δ8,9 blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of Δ9 and Δ8,9 in treating a human patient inflicted with Crohn's disease.

What is claimed is: 
     
         1 . A method of inhibiting IL-23R-mediated cell signaling in a mammalian cell, comprising the steps of:
 a) providing a mammalian cell in need thereof;   b) providing a recombinant IL-23Rα protein, said recombinant IL-23Rα protein has an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4; and   c) exposing said mammalian cell to an effective amount of said recombinant IL-23Rα protein, thereby inhibits IL-23R mediated cell signaling in said mammalian cell.   
     
     
         2 . The method of  claim 1 , wherein said recombinant IL-23Rα protein has an amino acid sequence consisting of SEQ ID NO: 2. 
     
     
         3 . The method of  claim 1 , wherein said recombinant IL-23Rα protein has an amino acid sequence consisting of SEQ ID NO: 4. 
     
     
         4 . The method of  claim 1 , wherein said IL-23 mediated cell signaling is phosphorylation of STAT1, STAT2, STAT3, or STAT5. 
     
     
         5 . The method of  claim 1 , wherein said IL-23 mediated cell signaling is phosphorylation of STAT3. 
     
     
         6 . The method of  claim 1 , wherein said IL-23 mediated cell signaling is secretion of IL-17A or IL-17F. 
     
     
         7 . The method of  claim 1 , wherein said IL-23 mediated cell signaling is secretion of IL-17A. 
     
     
         8 . The method of  claim 1 , wherein said IL-23 mediated cell signaling is Th-17 cell maturation. 
     
     
         9 . The method of  claim 1 , wherein said mammalian cell is a human cell. 
     
     
         10 . The method of  claim 1 , wherein said mammalian cell is 293T cell.