Wilfried Ellmeier, PhD
Center for Physiology and Pathophysiology
T lymphocytes (T cells) are key cellular players in the regulation and execution of immune responses in response to foreign pathogens. However, dysregulation of effector T cell function is linked with the development of immune-mediated diseases such as autoimmunity or allergy. Thus, the activity of T cells has to be tightly controlled. Our long-term research interest is to characterize molecular mechanisms that regulate the development and function of T lymphocytes. We made important contributions to the transcriptional control of Cd8 gene expression and identified that the transcription factor MAZR is an important regulator of CD8 expression as well as of CD4/CD8 lineage development. Moreover, we are interested in elucidating the roles of histone deacetylases (HDACs) in T cells and e.g. we recently identified that CD4+ T cell lineage integrity is regulated by HDAC1 and HDAC2. Further, we have also a long-standing interest in revealing the role of Tec family kinases in the regulation of immune responses. With our studies we aim to provide important and medical relevant insight into the regulation of T cell-mediated immunity. In ongoing studies we are addressing topics like:
• Transcriptional control of CD4/CD8 cell fate choice.
• Molecular control of innate-like T cell lineage differentiation
• Transcription factor networks regulating peripheral T cell function.
• Maintenance of T cell lineage identity and integrity.
• Characterization of signaling pathways modulating Th differentiation.
The experimental strategies to address our research interests include multi-color flow-cytometry, a variety of immunological tools, biochemical and molecular approaches, retroviral-mediated gene transduction into hematopoietic stem cells, next generation sequencing and mouse molecular genetics tools.
Sakaguchi, S., D. Hainberger, C. Tizian, H. Tanaka, T. Okuda, I. Taniuchi, and W. Ellmeier. 2015. MAZR and Runx Factors Synergistically Repress ThPOK during CD8+ T Cell Lineage Development. J Immunol. 195(6):2879-87.
Boucheron, N, Tschismarov, R, Goeschl, L, Moser, Mirjam, Lagger, S, Sakaguchi, S, Winter, Lenz, F, Vitko, D., Breitwieser, FP, Haust, L, Hassan, H, Bennett, KL, Colinge, J, Schreiner, W, Matthias, P, Egawa, T, Taniuchi, I, Matthias, P, Seiser, C* and Ellmeier, W.* (2014). CD4 T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2. Nature Immunology, 15(5):439-48. (*shared senior-authorship)
Ellmeier, W., Haust, L., Tschismarov, R. (2013) Transcriptional control of CD4 and CD8 coreceptor expression during T cell development. Cellular and Molecular Life Sciences, 10.1007/s00018-013-1393-2
Hassan, H., Sakaguchi, S., Tenno, M., Kopf, A., Boucheron, N. Carpenter, A., Egawa, T., Taniuchi, I. Ellmeier, W. (2011) Cd8 enhancer E8I and Runx factors regulate CD8α expression in activated CD8+ T cells. PNAS, 108(45):18330-5.
Sakaguchi S, Hombauer M, Bilic I, Naoe Y, Schebesta A, Taniuchi I, Ellmeier, W. (2010). The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes. Nature Immunology, 11:442-8.