MiRNome and transcriptome aided pathway analysis in human regulatory T cells

• Published in: Genes and immunity Vol. 15; no. 5; pp. 303 - 312
• Main Authors: Albert, M H, Mannert, J, Fleischmann, K K, Schiemann, M, Pagel, P, Schmid, I, Magg, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2014; Nature Publishing Group
• Subjects: 38/39; 38/61; 631/250/2502/2055; Biology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Gene Expression; Gene Expression Profiling; Genes; Genetic aspects; Genetic engineering; Genetic research; Genetic transcription; Growth factors; Hematology; Human Genetics; Humans; Immunology; Immunoregulation; Janus kinase; Kinases; Lymphocyte Activation - genetics; Lymphocytes; Lymphocytes T; Messenger RNA; MicroRNA; MicroRNAs - genetics; Oncology; original-article; Pediatrics; Properties; Rapamycin; RNA, Messenger - genetics; Signal Transduction; T cell receptors; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Toll-like receptors; TOR protein; Transcription factors; Transcriptome; Transcriptomes; Transforming growth factor-b; Germany
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2014.20

Owing to their manifold immune regulatory functions, regulatory T cells (Treg) have received tremendous interest 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 with 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 T-cell receptor-, Toll-like receptor-, transforming growth factor-β-, JAK/STAT (Janus kinase/signal transducers and activators of transcription)- and mammalian target of rapamycin 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 functions.