Methods of treatment with antagonists of MU-1
Provided is a method of suppressing an immune response in a subject by administering an antagonist of a MU-1 hematopoietin receptor superfamily chain protein.
1. A method of suppressing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of a soluble polypeptide, wherein said polypeptide is encoded by a polynucleotide that hybridizes under stringent conditions of 0.1×SSC, 65° C. to the complement of the nucleotide sequence set forth in SEQ ID NO:1, and wherein said polypeptide binds IL-21.
2. The method of claim 1 , wherein said subject has an autoimmune disorder.
3. The method of claim 2 , wherein said autoimmune disorder is selected from the group consisting of rheumatoid arthritis, and systemic lupus erythematosus.
4. The method of claim 3 , wherein said autoimmune disorder is rheumatoid arthritis.
5. The method of claim 3 , wherein said autoimmune disorder is systemic lupus erythematosus.
6. The method of claim 1 , wherein said subject has Crohn's disease or IBD.
7. The method of claim 1 , wherein said immune response is to a transplanted organ.
8. The method of claim 1 , wherein said soluble polypeptide comprises from about amino acid 22 to about amino acid 236 of SEQ ID NO:2.
9. The method of claim 1 , wherein said soluble polypeptide comprises from about amino acid 1 to about amino acid 236 of SEQ ID NO:2.
10. The method of claim 1 , 8 , or 9 , wherein said soluble polypeptide is a fusion protein.
11. The method of claim 10 , wherein said fusion protein comprises an antibody fragment.
12. The method of claim 11 , wherein said antibody fragment is an Fc fragment.
13. The method of claim 1 , wherein said subject is a human.
14. The method of claim 12 , wherein said subject has rheumatoid arthritis.
15. A method of suppressing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of an antagonistic antibody that binds specifically to the amino acid sequence set forth in SEQ ID NO:2.
16. The method of claim 15 , wherein said subject has an autoimmune disorder.
17. The method of claim 16 , wherein said autoimmune disorder is selected from the group consisting of rheumatoid arthritis, and systemic lupus erythematosus.
18. The method of claim 16 , wherein said autoimmune disorder is rheumatoid arthritis.
19. The method of claim 16 , wherein said autoimmune disorder is systemic lupus erythematosus.
20. The method of claim 15 , wherein said subject has Crohn's disease or IBD.
21. The method of claim 15 , wherein said immune response is to a transplanted organ.
22. The method of claim 15 , wherein said antibody is a neutralizing antibody.
23. The method of claim 15 , wherein said antibody is a monoclonal antibody.
24. The method of claim 15 , wherein said subject is a human.
25. A method of suppressing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of a soluble polypeptide, wherein said polypeptide comprises at least 90 contiguous amino acid residues of the amino acid of SEQ ID NO:2.
26. The method of claim 25 , wherein said polypeptide comprises at least 100 contiguous amino acid residues of the amino acid of SEQ ID NO:2.
27. A method of suppressing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of a soluble polypeptide, wherein said polypeptide is a fusion polypeptide comprising a soluble fragment of a MU-1 protein, wherein said soluble fragment comprises at least 90 contiguous amino acid residues of the amino acid sequence of SEQ ID NO:2 linked to a heterologous polypeptide.
28. The method of claim 27 , wherein said soluble fragment comprises at least 100 contiguous amino acid residues of the amino acid sequence of SEQ ID NO:2 linked to a heterologous polypeptide.
29. The method of claim 28 , wherein said heterologous polypeptide is an antibody fragment.
30. The method of claim 29 , wherein, said antibody fragment is an Fc fragment.
31. The method of claim 27 , wherein said subject has an autoimmune disorder.
32. The method of claim 31 , wherein said autoimmune disorder is selected from the group consisting of rheumatoid arthritis, and systemic lupus erythematosus.
33. The method of claim 31 , wherein said autoimmune disorder is rheumatoid arthritis.
34. The method of claim 31 , wherein said autoimmune disorder is systemic lupus erythematosus.
35. The method of claim 27 , wherein said subject has Crohn's disease or IBD.
36. The method of claim 27 , wherein said immune response is to a transplanted organ.
37. The method of any of claims 1 , 15 , 25 , or 27 , further comprising administering to the subject a therapeutic agent selected from the group consisting of a cytokine inhibitor, a growth factor inhibitor, an immunosuppressant, an anti-inflammatory agent, a metabolic inhibitor, an enzyme inhibitor, a cytotoxic agent, and a cytostatic agent.
38. The method of claim 37 , wherein the therapeutic agent is selected from the group consisting of a TNF antagonist, an IL-12 antagonist, an IL-15 antagonist, an IL-17 antagonist, an IL-18 antagonist, an IL-22 antagonist, a T cell-depleting agent, a B cell-depleting agent, methotrexate, leflunomide, rapamycin or an analog thereof, FK506, cyclosporine, a Cox-2 inhibitor, a cPLA2 inhibitor, an NSAID, and a p38 inhibitor.