Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Upon antigen encounter naive CD4+ T helper (Th) cells differentiate into distinct T helper cell subsets characterized by specific cytokine and transcription factor expression. It is currently debated whether these Th subsets have a fixed or flexible phenotype. Previously we showed that in the course of viral infection Th2 cells can be reprogrammed into a hybrid Th2+1 phenotype co-expressing Th1 and Th2 key transcription factors and cytokines. However, the T cell intrinsic control of subset-specific gene expression is only partially understood. Studies have indicated that post-transcriptional regulation via microRNA contributes to several aspects of T cell gene expression. Nevertheless, only few relevant miRNAs have been described so far. The aim of this project is to identify miRNA specifically expressed in novel hybrid T cell phenotypes as well as to analyze their impact on T cell plasticity and function. We used microarray analysis to identify 22 differentially expressed miRNAs in hybrid Th2+1 cells compared to both Th1 and Th2 cells. Within this subset 8 miRNAs were up and 11 miRNAs were down regulated. We found that type I IFNs are potent inducers of some of these miRNAs. Additionally, we observed an inverse correlation in expression of some miRNAs with their predicted targets that are known for their role in Th cell activation and differentiation. Overall, these miRNAs could prove to be important players in the induction and maintenance of Th2+1 cells.</jats:p>