THERAPEUTIC APPLICATION OF ISOLATED NATURALLY-OCCURRING SOLUBLE TRUNCATED FORMS OF IL-23 RECEPTOR
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.
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.