Micro-rnas modulating immunity and inflammation

Abstract

MicroRNAs are shown to be up- and/or down-regulated in inflammation and immune cells using a mouse model of asthma and regulatory T cells as source of RNA, respectively. Modulating the expression of these microRNAs can be effective in redirecting inflammation and immunity and hence, can be beneficial as biomarkers or as therapeutic agents against diverse human immunologic and inflammatory diseases.

What is claimed is: 
     
         1 . A method for screening for asthma in a subject comprising the steps of:
 assaying the miRNA expression level in a test sample of cells or tissue from the subject to be screened for asthma;   comparing the assayed the miRNA expression level to the miRNA expression level in a normal sample providing a control relative to the test sample of the subject; and   computing the differential expression of the miRNA from the subject.   
     
     
         2 . The method according to  claim 1 , wherein the assayed miRNA is miR-765, miR-711, miR-690, miR-709, miR-762, miR-296, miR-671, miR-680, miR-760, miR-710, miR-320, miR-770-3p, miR-601, miR-577, miR-340, miR-326, miR-515-3p, miR-494, miR-142-3p, miR-705, miR-674, let-7f, miR-466, miR-540, miR-702, miR-584, miR-505, miR-17-3p, miR-721, miR-202, miR-564, miR-759, miR-638, miR-295, miR-325, miR-470, miR-573, miR-206, miR-298, miR-671, miR-198, miR-370, miR-320, miR-766, miR-610, let-7d, let-7b, let-7a, miR-150, miR-630, miR-185, miR-659, miR-625, miR-214, miR-493-3p, miR-296, miR-513, miR-768-5p, miR-637, miR-551a, let-7c, miR-542-5p, miR-320, miR-611, miR-381, miR-328, miR-518c, miR-27a, miR-608, miR-30d, hsa-miR-575, miR-21, or miR-658. 
     
     
         3 . The method according to  claim 1 , wherein at least one of the miRNAs assayed is an asthma-associated miRNA under-expressed in asthma. 
     
     
         4 . The method according to  claim 3 , wherein the under-expressed miRNA is miR-690, miR-709, miR-762, miR-320, miR-494, miR-142-3p, let-7f, miR-550, miR-759, miR-573, miR-150, miR-214, miR-637, let7c, miR-381, miR-27a, or miR-575. 
     
     
         5 . The method according to  claim 1 , wherein at least one of the miRNAs assayed is an asthma-associated miRNA over-expressed in asthma. 
     
     
         6 . The method according to  claim 5 , wherein the over-expressed miRNA is miR-760, miR-515-3p, or miR-671. 
     
     
         7 . A method of identifying miRNA biomarkers of immunologic disease comprising the steps of:
 generating an miRNA expression profile for a test sample representative of the immunologic disease;   generating an miRNA expression profile for a control sample not exhibiting the disease; and   comparing the miRNA expression profile of the test sample with the miRNA expression profile of control sample, wherein the differential expression of the miRNA identifies potential miRNA biomarkers for immunologic disease.   
     
     
         8 . A method for treating inflammation or an immunologic disorder comprising the step of contacting a cell or cells with an agent that modulates the expression of one or more miRNA in the cell. 
     
     
         9 . The method according to  claim 8 , wherein the agent up-regulates the expression of at least one of the one or more miRNA. 
     
     
         10 . The method according to  claim 9 , wherein the agent is a vector comprising an miRNA sequence, or a derivative or analog thereof, underexpressed in the associated disease. 
     
     
         11 . The method according to  claim 10 , wherein the underexpressed miRNA is miR-690, miR-709, miR-762, miR-320, miR-494, miR-142-3p, let-7f, miR-550, miR-759, miR-573, miR-150, miR-214, miR-637, let7c, miR-381, miR-27a, or miR-575. 
     
     
         12 . The method according to  claim 8 , wherein the agent down-regulates the expression of at least one of the one or more miRNA. 
     
     
         13 . The method according to  claim 12 , wherein the agent is a vector comprising an miRNA sequence, or a derivative or analog thereof, overexpressed in the associated disease. 
     
     
         14 . The method according to  claim 12 , wherein the agent is an antisense RNA to the overexpressed miRNA. 
     
     
         15 . The method according to  claim 13 , wherein the over-expressed miRNA is miR-760, miR-515-3p, or miR-671. 
     
     
         16 . The method according to  claim 8 , wherein the immunologic disorder is asthma.