Methods and compositions for mitigating eosinophilic esophagitis by modulating levels and activity of eotaxin-3

Abstract

Eotaxin-3, as a marker for eosinophilic esophagitis and methods of assessing, mitigating, and monitoring eosinophilic esophagitis by altering eotaxin-3 and/or CCR3 function, are disclosed.

1 - 12 . (canceled) 
     
     
         13 . A method to mitigate eosinophilic esophagitis comprising:
 providing an inhibitor to at least one of eotaxin-3 or a receptor for binding eotaxin-3 in a cell under conditions sufficient to inhibit eotaxin-3 binding to the receptor.   
     
     
         14 . The method of  claim 13 , wherein the cell is an eosinophil. 
     
     
         15 . The method of  claim 13 , wherein the cell is a mast cell. 
     
     
         16 . The method of  claim 13 , wherein the receptor is CCR3 and the inhibitor is a CCR3 antagonist. 
     
     
         17 . The method of  claim 16 , wherein the CCR3 antagonist is selected from the group consisting of MIG, I-TAC, IP-10, vMIP-II, met-RANTES, a carboxamide derivative, a 2-(Benzothiazolylthio)acetamide derivative, a piperidine derivative, and UCB35625, SK&F- L -45523, and derivatives thereof. 
     
     
         18 . The method of  claim 13 , wherein the inhibitor is a small molecule inhibitor. 
     
     
         19 . The method of  claim 13 , wherein the inhibitor inhibits at least one of transcription or translation of eotaxin-3 or CCR3, or combinations thereof. 
     
     
         20 . The method of  claim 13 , wherein the inhibitor is selected from the group consisting of an inducer of CCR3 desensitization, an inducer of CCR3 internalization, and a small molecule inhibitor of CCR3. 
     
     
         21 . The method of  claim 13 , wherein the inhibitor is selected from the group consisting of a humanized antibody against at least one of eotaxin-3 or CCR3, a human antibody against at least one of eotaxin-3 or CCR3, and combinations thereof. 
     
     
         22 . The method of  claim 13 , wherein the inhibitor is selected from the group consisting of a CCR3 signal transduction inhibitor, and a transcriptional inhibitor selected from the group consisting of an antisense oligonucleotide, a transcription factor inhibitor, and combinations thereof. 
     
     
         23 . The method of  claim 13 , wherein the inhibitor includes a recombinant polypeptide including at least 70% identity to a full length murine eotaxin cDNA, full length guinea pig eotaxin cDNA, or human eotaxin DNA. 
     
     
         24 . The method of  claim 13 , wherein the inhibitor is selected from the group consisting of an anti-eotaxin-3 antibody or fragment thereof, an immunologically active antibody fragment, a genetically engineered antibody fragment, and a purified antibody, and wherein the purified antibody is selected from the group consisting of an intact monoclonal antibody and an intact polyclonal antibody. 
     
     
         25 . The method of  claim 13 , wherein the inhibitor includes an eotaxin polypeptide having a deletion of 1-10 N-terminal amino acids or an addition of 3-10 amino acids on the amino terminus.