MiRNome and transcriptome aided pathway analysis in human regulatory T cells

Owing to their manifold immune regulatory functions, regulatory T cells (Treg) have received tremendous interests as targets for therapeutic intervention of diverse immunological pathologies or cancer. Directed manipulation of Treg will only be achievable with extensive knowledge about the intrinsic programs that define their regulatory function. We simultaneously analyzed miR and mRNA transcript levels in resting and activated human Treg cells in comparison to non-regulatory conventional T cells (Tcon). Based on experimentally validated miR-target information, both transcript levels were integrated into a comprehensive pathway analysis. This strategy revealed characteristic signal transduction pathways involved in Treg biology such as TCR-, TLR-, TGF-, JAK/STAT- and mTOR signaling and allowed for the prediction of specific pathway activities on the basis of miR and mRNA transcript levels in a probabilistic manner. These data encourage new concepts for targeted control of Treg cell effector function. Differential gene expression was measured in highly pure, FACS-sorted, resting regulatory T cells and conventional T cells and stimulated regulatory T cells and conventional T cells. Two independent experiments using pooled samples from 5 different donors were performed for each cell type and activation condition.