T lymphocytes (T cells) are key cellular players in the regulation and execution of immune responses in response to foreign pathogens and also against endogenous danger such as cancer cells. Naïve CD4+ T cells will, upon activation by antigen-presenting cells (APC), differentiate into various effector T helper (Th) subsets including Th1, Th2, Th17, Tfh and peripherally induced regulatory T cells (pTreg) cell subsets. The type of effector Th cell generated depends on the nature of the antigenic stimulus and the cytokine microenvironment at the site of antigen recognition. Each lineage is characterized by a set of key transcription factors and distinct cytokine expression profiles, although Th subset lineage identity is not fixed and plasticity of Th cells has been demonstrated. Due to their distinct cytokine profile, each subset fulfills specific functions and is essential for the efficient elimination of particular types of pathogens such as extracellular and intracellular bacteria, fungi or helminths. Moreover, some subsets (i.e. regulatory T cells) are essential for regulating immune tissue homeostasis and self-tolerance. Similarly, naïve CD8+ T cells have to be activated to acquire their cytotoxic effector functions. The activation processes of CD4+ and CD8+ T cells have to be tightly regulated, since dysregulation of effector T cell differentiation and function is linked with the development of immune-mediated diseases such as allergy, chronic inflammation and autoimmunity. Molecular and cellular insight into the control of T cell function is therefore of high medical relevance. The possibility for specific manipulation of T cell responses might be crucial for dampening immune responses in autoimmune diseases and in transplantation settings, for boosting T cell-mediated immunity during infection and to improve vaccination strategies, or for enhancing T cell responses to fight cancer cells.
Our long-term research interest is to characterize molecular mechanisms that regulate the development and function of T lymphocytes. With our studies we aim to provide important and medical relevant insight into the regulation of T cell-mediated immunity. In ongoing studies we address the following research topics:
• The role of histone deacetylases in the regulation of T cell-mediated immunity
• Transcriptional control of T cell development
• Regulation of peripheral T cell function and maintenance of T cell lineage identity and integrity
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.