Method of regulating nfatc2 activity in lymphocytes

Abstract

A method of decreasing NFATc2 activity in a lymphocyte includes administering to the lymphocyte an amount of an NFATc2 mRNA antagonist that binds to a binding site on the 3′UTR of NFATc2 mRNA effective to decrease the activity of NFATc2 mRNA in the lymphocyte.

Having described the invention, the following is claimed: 
     
         1 . A method of decreasing NFATc2 activity in a lymphocyte, comprising administering to the lymphocyte an amount of an NFATc2 mRNA antagonist that binds to a binding site on the 3′UTR of NFATc2 mRNA effective to decrease the activity of NFATc2 mRNA in the lymphocyte. 
     
     
         2 . The method of  claim 1 , the NFATc2 mRNA antagonist comprising microRNA directed to NFATc2 mRNA. 
     
     
         3 . The method of  claim 2 , the microRNA specifically binding to a nucleotide sequence substantially homologous with SEQ ID NO: 2. 
     
     
         4 . The method of  claim 3 , the microRNA consisting essentially of a nucleotide sequence substantially homologous to SEQ ID NO:1. 
     
     
         5 . The method of  claim 1 , the lymphocyte comprising a CD4 + T cell. 
     
     
         6 . The method of  claim 1 , wherein the CD4 + T cell is administered to the bone marrow of a subject. 
     
     
         7 . The method of  claim 6 , wherein the CD4 + T cell is administered in a transplantable material. 
     
     
         8 . The method of  claim 6 , wherein the CD4 + T cell is not endogenous to the subject. 
     
     
         9 . The method of  claim 8 , wherein the CD4 + T cell, or a progenitor cell thereof, has been transplanted into the subject. 
     
     
         10 . A method of decreasing NFATc2 expression in a lymphocyte, comprising administering to the lymphocyte an amount of an NFATc2 mRNA antagonist effective to decrease the activity of NFATc2 mRNA in the lymphocyte, the NFATc2 antagonist comprising microRNA having nucleotide sequence substantially homologous to SEQ ID NO:1. 
     
     
         11 . The method of  claim 10 , the lymphocyte comprising a CD4 + T cell. 
     
     
         12 . The method of  claim 10 , wherein the CD4 + T cell is administered to the bone marrow of a subject. 
     
     
         13 . The method of  claim 12 , wherein the CD4 + T cell is administered in a transplantable material. 
     
     
         14 . The method of  claim 11 , wherein the CD4 + T cell is not endogenous to the subject. 
     
     
         15 . The method of  claim 11 , wherein the CD4 + T cell, or a progenitor cell thereof, has been transplanted into the subject. 
     
     
         16 . A method of preventing or reducing immune incompatibility in a subject, the method comprising administering to the subject or tissue transplanted to the subject a therapeutically effective amount of an NFATc2 antagonist, the NFATc2 antagonist comprising microRNA having nucleotide sequence substantially homologous to SEQ ID NO:1. 
     
     
         17 . The method of  claim 16 , wherein the subject has or is at risk for having graft versus host disease. 
     
     
         18 . The method of  claim 16 , wherein the subject has or is at risk for having graft rejection. 
     
     
         19 . The method of  claim 16 , wherein the subject is the recipient of a transplant. 
     
     
         20 . The method of  claim 16 , wherein the subject is the recipient of a hematopoietic stem cell transplant.