Treatment of Inflammation, Autoimmune, and Neurodegenerative Disorders with Immunosuppressive Tat Derivative Polypeptides

Abstract

The present specification provides immunosuppressive Tat derivative polypeptides, compositions, and methods of using such polypeptides and compositions to treat an autoimmune disease, an inflammation-associated disease and/or a neurodegenerative disease.

What is claimed is: 
     
         1 . An immunosuppressive trans-activator of transcription (Tat) derivative polypeptide comprising an amino acid sequence comprising the following domains in the indicated order:
 a transcription factor (TF) domain comprising SEQ ID NO: 39;   a cysteine-rich region comprising SEQ ID NO: 65; and   a C-terminal region comprising amino acid residues 18-70 of SEQ ID NO: 42.   
     
     
         2 . The immunosuppressive trans-activator of transcription (Tat) derivative polypeptide of  claim 1  comprising SEQ ID NO: 9. 
     
     
         3 . The immunosuppressive Tat derivative polypeptide of  claim 1 , wherein the TF domain further comprises a repeat sequence comprising (PVDPRLEPWKHPGSQP) n  (SEQ ID NO: 12) at the N-terminus, wherein n=2-10. 
     
     
         4 . A pharmaceutical composition comprising the immunosuppressive Tat derivative polypeptide according to  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         5 . A method of treating a disease characterized by aberrant immune responses, the method comprising:
 administering a therapeutically effective amount of the pharmaceutical composition of  claim 4 .   
     
     
         6 . A method of increasing the expression of Fas ligand (FasL) on antigen presenting cell regulatory macrophages (ARegs) comprising:
 administering a therapeutically effective amount of the pharmaceutical composition of  claim 4 .   
     
     
         7 . A method of reducing inflammation, the method comprising:
 administering a therapeutically effective amount of the pharmaceutical composition of  claim 4 .