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 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.
Department of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital, Munich, Germany.
M H
MH
Albert
Department of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital, Munich, Germany.
J
J
Mannert
Department of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital, Munich, Germany.
K K
KK
Fleischmann
1] Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany [2] Immune-Monitoring and Clinical Cooperation Groups 'Antigen-specific Immunotherapy', Helmholtz Center Munich (Neuherberg), Munich, Germany.
M
M
Schiemann
Lehrstuhl für Genomorientierte Bioinformatik Technische Universität München, Munich, Germany.
P
P
Pagel
Department of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital, Munich, Germany.
I
I
Schmid
Department of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital, Munich, Germany.
T
T
Magg
D020869:Gene Expression Profiling; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D059467:Transcriptome
D035683:MicroRNAs; D012333:RNA, Messenger