Absence of miR-182 Augments Cardiac Allograft Survival.

Background: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. Methods: Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182-/-, B6.129S-H2dlAb1-Ea (MHC II- and CD4+ T cell-deficient) and B6.129S2-Tap1tm1Arp (MHC I- and CD8+ T cell-deficient) mice, with or without CTLA-4Ig administration. T cell phenotype, FOXO1 protein levels and graft infiltrating lymphocytes were determined in C57BL/6 or miR-182-/- mice by flow cytometric analysis, western blot and immunohistochemistry, respectively. Results: We now show that T cells, mainly CD4+ are the main cellular source of miR-182 during allograft rejection. In the absence of miR-182, CTLA-4Ig treatment significantly increased allograft survival (31.5 days C57BL/6 vs. 60 days miR-182-/-, P

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