TRR 52:  Transcriptional Programming of Individual T Cell Subsets

• Subject Area: Medicine ; Biology
• Term: from 2008 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 34528275

The long-term research aim of the Transregional Collaborative Research Centre is to gain new scientific insights into the function of T lymphocytes. We aim to bring together different fields of expertise in T cell biology of laboratories in Würzburg, Mainz and Berlin. The expected findings will significantly broaden our insight into the regulation of transcription in T cells. In the future, a deepened understanding will contribute to the development of more specific therapies for frequent disorders of the immune system, above all autoimmune diseases.
T lymphocytes control the adaptive immune system and are, therefore, the subject of intense biomedical research worldwide. After selection in the thymus, T lymphocytes mature in peripheral lymphoid organs to various T effector cells. Type 1 and type 2 T helper (Th1 and Th2) cells have been characterised in the past, more recently Th17, follicular Th (ThFH), regulatory T helper (Treg) cells, and other T cell subsets have been described. If deregulated, this complex network of T cell subsets leads to the development of autoimmune and allergic disorders. Basic research as well as (pre-)clinical work suggest that Treg cells are one of the central elements in maintaining the balance between self-tolerance and autoimmunity. Therefore, one major aspect of the experimental work in the Transregional Collaborative Research Centre will be the analysis of numerous aspects of Treg (molecular) biology.
Most of currently available data in the field of transcriptional control emerged from "static endpoint experiments" in vitro, which were often performed with cell lines. These types of experiments do not provide accurate information on the regulatory dynamics of gene regulation in immune cells in vivo. Therefore, a further major goal of the Transregional Collaborative Research Centre is to overcome the limitations of in vitro work. By bringing together laboratories with a strong background in transcription analysis with laboratories working on T cell biology in vivo we intend to catalyse a transfer of concepts and technologies in both directions. The Transregional Collaborative Research Centre shall also become an ideal ground for the training of a new generation of researchers who will be able to tackle these new challenges in their future work.
We are convinced that the work in the Transregional Collaborative Research Centre will provide a deepened scientific basis for the development of novel therapies of autoimmune and allergic diseases. With our research work we hope to contribute to the development of even better and more specific therapies in the future.

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Transcription Factors of Murine Regulatory T Cells and Suppressed CD4+ T Cells: Identification and Functional Analyses (Project Heads Bopp, Tobias ;  Schmitt, Edgar )
• A02 - Analysis of Differential Gene Expression and Signal Transduction in Human Regulatory T Cells (Project Heads Jonuleit, Helmut ;  Ohlemacher, Sabine ;  Tüttenberg, Andrea Renate )
• A03 - Repression of Gene Expression in T-Lymphocytes Mediated by Multi-Protein Complexes of Chosen Transcription Factors (Project Heads Berberich-Siebelt, Friederike ;  Jonuleit, Helmut ;  Sickmann, Albert )
• A04 - Regulation of Foxp3 Expression (Project Heads Hamann, Alf ;  Hühn, Jochen )
• A05 - The Role of CD28-mediated Signals in the Generation, Homeostasis and Function of Regulatory T-cells (Project Head Hünig, Thomas )
• A07 - Transcriptional Regulation of IL-2 Expression in Human Regulatory T Cells (Project Head Steinbrink, Kerstin )
• A08 - Functional Characterization of New Regulatory RUNX1 (AML1) Isoforms in T Cells (Project Heads Gattenlöhner, Stefan ;  Schmitt, Edgar )
• B01 - Binary Decision Making in Gene Expression Control of T Lymphocytes (Project Heads Baumgraß, Ria ;  Radbruch, Andreas )
• B02 - NFAT Transcription Factors as Sensors and Switch Factors of Lymphopoiesis in vivo (Project Heads Avots, Andris ;  Serfling, Edgar )
• B04 - Epigenetic Control of the Transcription of Homing Receptors (Project Heads Hamann, Alf ;  Syrbe, Uta )
• B05 - Transcriptional Regulation of the Human and Mouse TNF/Lymphotoxin Locus in T Lymphocytes of Transgenic and Knock-in Mice (Project Head Nedospasov, Sergei A. )
• B06 - Programming of CD4+ T Cells for (Memory) Immune Response versus Tolerance in vivo (Project Head Kroczek, Richard )
• B07 - Tolerogenic and Immunogenic T Helper 2 Programming by Differentially Matured Dendritic Cells (Project Head Lutz, Manfred )
• B08 - Transcriptional Control of Follicular T Helper Cell (TFH) Differentiation by Notch- and bHLH Proteins (Project Heads Lipp, Martin ;  Müller, Gerd )
• C01 - Immunoregulatory Role of Nuclear Factor of Activated T Cells (NFAT) and NFAT Interacting Protein- NIP45- in Allergic Asthma (Project Head Finotto, Ph.D., Susetta )
• C02 - Regulatory T Cells and Th17 Cells in Autoimmune Brain Inflammation (Project Head Waisman, Ari )
• C03 - Transcriptional Regulation and Pathogenetic Relevance of IL-28/IL-29 Cytokine System in Colitis and Colitis Associated Colon Carcinoma (Project Heads Neurath, Markus F. ;  Siebler, Juergen )
• C04 - Importance of Toag-1 and Smarca3 for the Transcriptional Regulation of T Cells (Project Heads Sawitzki, Birgit ;  Volk, Hans-Dieter )
• C05 - Molecular Mechanisms Controling NFATc1 Transcription in Lymphoid Cells in vivo (Project Heads Avots, Andris ;  Serfling, Edgar )
• V01 - Central Tasks of the Collaborative Research Centre/Secretariat (Project Head Schmitt, Edgar )
• Z01 - Genetic Manipulation of Mice and Generation of Humanized Mice (Project Heads Reifenberg, Kurt ;  Waisman, Ari )
• Z02 - In vivo Imaging (Project Head Beilhack, Andreas )

• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Co-Applicant Institution: Charité - Universitätsmedizin Berlin; Julius-Maximilians-Universität Würzburg
• Participating Institution: Deutsches Rheuma-Forschungszentrum Berlin (DRFZ); Max-Delbrück-Centrum für Molekulare Medizin (MDC); Robert Koch-Institut (RKI)
• Spokesperson: Professor Dr. Edgar Schmitt